Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability
The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodi...
Ausführliche Beschreibung
Gespeichert in:
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2019transfer abstract |
|---|
| Übergeordnetes Werk: |
Enthalten in: The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms - Heyden, Mariano L.M. ELSEVIER, 2022, official journal of the European Federation for Pharmaceutical Sciences, New York, NY [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:138 ; year:2019 ; day:1 ; month:10 ; pages:0 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ejps.2019.105015 |
|---|
| Katalog-ID: |
ELV047685891 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV047685891 | ||
| 003 | DE-627 | ||
| 005 | 20230626020201.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 191022s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejps.2019.105015 |2 doi | |
| 028 | 5 | 2 | |a GBV00000000000725.pica |
| 035 | |a (DE-627)ELV047685891 | ||
| 035 | |a (ELSEVIER)S0928-0987(19)30279-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 300 |a 330 |a 360 |q VZ |
| 084 | |a 85.05 |2 bkl | ||
| 084 | |a 85.06 |2 bkl | ||
| 084 | |a 89.52 |2 bkl | ||
| 100 | 1 | |a Guimarães, Daniel Silqueira Martins |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| 264 | 1 | |c 2019transfer abstract | |
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. | ||
| 520 | |a The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. | ||
| 700 | 1 | |a de Sousa Luz, Letícia Silveira |4 oth | |
| 700 | 1 | |a do Nascimento, Sara Batista |4 oth | |
| 700 | 1 | |a Silva, Lorena Rabelo |4 oth | |
| 700 | 1 | |a de Miranda Martins, Natália Rezende |4 oth | |
| 700 | 1 | |a de Almeida, Heloísa Gonçalves |4 oth | |
| 700 | 1 | |a de Souza Reis, Vitória |4 oth | |
| 700 | 1 | |a Maluf, Sarah El Chamy |4 oth | |
| 700 | 1 | |a Budu, Alexandre |4 oth | |
| 700 | 1 | |a Marinho, Juliane Aparecida |4 oth | |
| 700 | 1 | |a Abramo, Clarice |4 oth | |
| 700 | 1 | |a Carmona, Adriana Karaoglanovic |4 oth | |
| 700 | 1 | |a da Silva, Marina Goulart |4 oth | |
| 700 | 1 | |a da Silva, Gisele Rodrigues |4 oth | |
| 700 | 1 | |a Kemmer, Victor Matheus |4 oth | |
| 700 | 1 | |a Butera, Anna Paola |4 oth | |
| 700 | 1 | |a Ribeiro-Viana, Renato Márcio |4 oth | |
| 700 | 1 | |a Gazarini, Marcos Leoni |4 oth | |
| 700 | 1 | |a Júnior, Clébio Soares Nascimento |4 oth | |
| 700 | 1 | |a Guimarães, Luciana |4 oth | |
| 700 | 1 | |a dos Santos, Fabio Vieira |4 oth | |
| 700 | 1 | |a de Castro, Whocely Victor |4 oth | |
| 700 | 1 | |a Viana, Gustavo Henrique Ribeiro |4 oth | |
| 700 | 1 | |a de Brito, Cristiana Ferreira Alves |4 oth | |
| 700 | 1 | |a de Pilla Varotti, Fernando |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Heyden, Mariano L.M. ELSEVIER |t The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |d 2022 |d official journal of the European Federation for Pharmaceutical Sciences |g New York, NY [u.a.] |w (DE-627)ELV009954198 |
| 773 | 1 | 8 | |g volume:138 |g year:2019 |g day:1 |g month:10 |g pages:0 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ejps.2019.105015 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 936 | b | k | |a 85.05 |j Betriebssoziologie |j Betriebspsychologie |q VZ |
| 936 | b | k | |a 85.06 |j Unternehmensführung |q VZ |
| 936 | b | k | |a 89.52 |j Politische Psychologie |j Politische Soziologie |q VZ |
| 951 | |a AR | ||
| 952 | |d 138 |j 2019 |b 1 |c 1001 |h 0 | ||
| author_variant |
d s m g dsm dsmg |
|---|---|
| matchkey_str |
guimaresdanielsilqueiramartinsdesousaluz:2019----:mrvmnoatmlraatvtoaakliiielaodnlgyelcnteyiieigotizlcnannhtrcceoefcin |
| hierarchy_sort_str |
2019transfer abstract |
| bklnumber |
85.05 85.06 89.52 |
| publishDate |
2019 |
| allfields |
10.1016/j.ejps.2019.105015 doi GBV00000000000725.pica (DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 DE-627 ger DE-627 rakwb eng 300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Guimarães, Daniel Silqueira Martins verfasserin aut Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. de Sousa Luz, Letícia Silveira oth do Nascimento, Sara Batista oth Silva, Lorena Rabelo oth de Miranda Martins, Natália Rezende oth de Almeida, Heloísa Gonçalves oth de Souza Reis, Vitória oth Maluf, Sarah El Chamy oth Budu, Alexandre oth Marinho, Juliane Aparecida oth Abramo, Clarice oth Carmona, Adriana Karaoglanovic oth da Silva, Marina Goulart oth da Silva, Gisele Rodrigues oth Kemmer, Victor Matheus oth Butera, Anna Paola oth Ribeiro-Viana, Renato Márcio oth Gazarini, Marcos Leoni oth Júnior, Clébio Soares Nascimento oth Guimarães, Luciana oth dos Santos, Fabio Vieira oth de Castro, Whocely Victor oth Viana, Gustavo Henrique Ribeiro oth de Brito, Cristiana Ferreira Alves oth de Pilla Varotti, Fernando oth Enthalten in Elsevier Heyden, Mariano L.M. ELSEVIER The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms 2022 official journal of the European Federation for Pharmaceutical Sciences New York, NY [u.a.] (DE-627)ELV009954198 volume:138 year:2019 day:1 month:10 pages:0 https://doi.org/10.1016/j.ejps.2019.105015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 85.05 Betriebssoziologie Betriebspsychologie VZ 85.06 Unternehmensführung VZ 89.52 Politische Psychologie Politische Soziologie VZ AR 138 2019 1 1001 0 |
| spelling |
10.1016/j.ejps.2019.105015 doi GBV00000000000725.pica (DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 DE-627 ger DE-627 rakwb eng 300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Guimarães, Daniel Silqueira Martins verfasserin aut Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. de Sousa Luz, Letícia Silveira oth do Nascimento, Sara Batista oth Silva, Lorena Rabelo oth de Miranda Martins, Natália Rezende oth de Almeida, Heloísa Gonçalves oth de Souza Reis, Vitória oth Maluf, Sarah El Chamy oth Budu, Alexandre oth Marinho, Juliane Aparecida oth Abramo, Clarice oth Carmona, Adriana Karaoglanovic oth da Silva, Marina Goulart oth da Silva, Gisele Rodrigues oth Kemmer, Victor Matheus oth Butera, Anna Paola oth Ribeiro-Viana, Renato Márcio oth Gazarini, Marcos Leoni oth Júnior, Clébio Soares Nascimento oth Guimarães, Luciana oth dos Santos, Fabio Vieira oth de Castro, Whocely Victor oth Viana, Gustavo Henrique Ribeiro oth de Brito, Cristiana Ferreira Alves oth de Pilla Varotti, Fernando oth Enthalten in Elsevier Heyden, Mariano L.M. ELSEVIER The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms 2022 official journal of the European Federation for Pharmaceutical Sciences New York, NY [u.a.] (DE-627)ELV009954198 volume:138 year:2019 day:1 month:10 pages:0 https://doi.org/10.1016/j.ejps.2019.105015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 85.05 Betriebssoziologie Betriebspsychologie VZ 85.06 Unternehmensführung VZ 89.52 Politische Psychologie Politische Soziologie VZ AR 138 2019 1 1001 0 |
| allfields_unstemmed |
10.1016/j.ejps.2019.105015 doi GBV00000000000725.pica (DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 DE-627 ger DE-627 rakwb eng 300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Guimarães, Daniel Silqueira Martins verfasserin aut Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. de Sousa Luz, Letícia Silveira oth do Nascimento, Sara Batista oth Silva, Lorena Rabelo oth de Miranda Martins, Natália Rezende oth de Almeida, Heloísa Gonçalves oth de Souza Reis, Vitória oth Maluf, Sarah El Chamy oth Budu, Alexandre oth Marinho, Juliane Aparecida oth Abramo, Clarice oth Carmona, Adriana Karaoglanovic oth da Silva, Marina Goulart oth da Silva, Gisele Rodrigues oth Kemmer, Victor Matheus oth Butera, Anna Paola oth Ribeiro-Viana, Renato Márcio oth Gazarini, Marcos Leoni oth Júnior, Clébio Soares Nascimento oth Guimarães, Luciana oth dos Santos, Fabio Vieira oth de Castro, Whocely Victor oth Viana, Gustavo Henrique Ribeiro oth de Brito, Cristiana Ferreira Alves oth de Pilla Varotti, Fernando oth Enthalten in Elsevier Heyden, Mariano L.M. ELSEVIER The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms 2022 official journal of the European Federation for Pharmaceutical Sciences New York, NY [u.a.] (DE-627)ELV009954198 volume:138 year:2019 day:1 month:10 pages:0 https://doi.org/10.1016/j.ejps.2019.105015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 85.05 Betriebssoziologie Betriebspsychologie VZ 85.06 Unternehmensführung VZ 89.52 Politische Psychologie Politische Soziologie VZ AR 138 2019 1 1001 0 |
| allfieldsGer |
10.1016/j.ejps.2019.105015 doi GBV00000000000725.pica (DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 DE-627 ger DE-627 rakwb eng 300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Guimarães, Daniel Silqueira Martins verfasserin aut Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. de Sousa Luz, Letícia Silveira oth do Nascimento, Sara Batista oth Silva, Lorena Rabelo oth de Miranda Martins, Natália Rezende oth de Almeida, Heloísa Gonçalves oth de Souza Reis, Vitória oth Maluf, Sarah El Chamy oth Budu, Alexandre oth Marinho, Juliane Aparecida oth Abramo, Clarice oth Carmona, Adriana Karaoglanovic oth da Silva, Marina Goulart oth da Silva, Gisele Rodrigues oth Kemmer, Victor Matheus oth Butera, Anna Paola oth Ribeiro-Viana, Renato Márcio oth Gazarini, Marcos Leoni oth Júnior, Clébio Soares Nascimento oth Guimarães, Luciana oth dos Santos, Fabio Vieira oth de Castro, Whocely Victor oth Viana, Gustavo Henrique Ribeiro oth de Brito, Cristiana Ferreira Alves oth de Pilla Varotti, Fernando oth Enthalten in Elsevier Heyden, Mariano L.M. ELSEVIER The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms 2022 official journal of the European Federation for Pharmaceutical Sciences New York, NY [u.a.] (DE-627)ELV009954198 volume:138 year:2019 day:1 month:10 pages:0 https://doi.org/10.1016/j.ejps.2019.105015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 85.05 Betriebssoziologie Betriebspsychologie VZ 85.06 Unternehmensführung VZ 89.52 Politische Psychologie Politische Soziologie VZ AR 138 2019 1 1001 0 |
| allfieldsSound |
10.1016/j.ejps.2019.105015 doi GBV00000000000725.pica (DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 DE-627 ger DE-627 rakwb eng 300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Guimarães, Daniel Silqueira Martins verfasserin aut Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. de Sousa Luz, Letícia Silveira oth do Nascimento, Sara Batista oth Silva, Lorena Rabelo oth de Miranda Martins, Natália Rezende oth de Almeida, Heloísa Gonçalves oth de Souza Reis, Vitória oth Maluf, Sarah El Chamy oth Budu, Alexandre oth Marinho, Juliane Aparecida oth Abramo, Clarice oth Carmona, Adriana Karaoglanovic oth da Silva, Marina Goulart oth da Silva, Gisele Rodrigues oth Kemmer, Victor Matheus oth Butera, Anna Paola oth Ribeiro-Viana, Renato Márcio oth Gazarini, Marcos Leoni oth Júnior, Clébio Soares Nascimento oth Guimarães, Luciana oth dos Santos, Fabio Vieira oth de Castro, Whocely Victor oth Viana, Gustavo Henrique Ribeiro oth de Brito, Cristiana Ferreira Alves oth de Pilla Varotti, Fernando oth Enthalten in Elsevier Heyden, Mariano L.M. ELSEVIER The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms 2022 official journal of the European Federation for Pharmaceutical Sciences New York, NY [u.a.] (DE-627)ELV009954198 volume:138 year:2019 day:1 month:10 pages:0 https://doi.org/10.1016/j.ejps.2019.105015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 85.05 Betriebssoziologie Betriebspsychologie VZ 85.06 Unternehmensführung VZ 89.52 Politische Psychologie Politische Soziologie VZ AR 138 2019 1 1001 0 |
| language |
English |
| source |
Enthalten in The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms New York, NY [u.a.] volume:138 year:2019 day:1 month:10 pages:0 |
| sourceStr |
Enthalten in The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms New York, NY [u.a.] volume:138 year:2019 day:1 month:10 pages:0 |
| format_phy_str_mv |
Article |
| bklname |
Betriebssoziologie Betriebspsychologie Unternehmensführung Politische Psychologie Politische Soziologie |
| institution |
findex.gbv.de |
| dewey-raw |
300 |
| isfreeaccess_bool |
false |
| container_title |
The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |
| authorswithroles_txt_mv |
Guimarães, Daniel Silqueira Martins @@aut@@ de Sousa Luz, Letícia Silveira @@oth@@ do Nascimento, Sara Batista @@oth@@ Silva, Lorena Rabelo @@oth@@ de Miranda Martins, Natália Rezende @@oth@@ de Almeida, Heloísa Gonçalves @@oth@@ de Souza Reis, Vitória @@oth@@ Maluf, Sarah El Chamy @@oth@@ Budu, Alexandre @@oth@@ Marinho, Juliane Aparecida @@oth@@ Abramo, Clarice @@oth@@ Carmona, Adriana Karaoglanovic @@oth@@ da Silva, Marina Goulart @@oth@@ da Silva, Gisele Rodrigues @@oth@@ Kemmer, Victor Matheus @@oth@@ Butera, Anna Paola @@oth@@ Ribeiro-Viana, Renato Márcio @@oth@@ Gazarini, Marcos Leoni @@oth@@ Júnior, Clébio Soares Nascimento @@oth@@ Guimarães, Luciana @@oth@@ dos Santos, Fabio Vieira @@oth@@ de Castro, Whocely Victor @@oth@@ Viana, Gustavo Henrique Ribeiro @@oth@@ de Brito, Cristiana Ferreira Alves @@oth@@ de Pilla Varotti, Fernando @@oth@@ |
| publishDateDaySort_date |
2019-01-01T00:00:00Z |
| hierarchy_top_id |
ELV009954198 |
| dewey-sort |
3300 |
| id |
ELV047685891 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV047685891</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626020201.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">191022s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejps.2019.105015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000725.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV047685891</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0928-0987(19)30279-9</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">300</subfield><subfield code="a">330</subfield><subfield code="a">360</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">85.05</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">85.06</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">89.52</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Guimarães, Daniel Silqueira Martins</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019transfer abstract</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Sousa Luz, Letícia Silveira</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">do Nascimento, Sara Batista</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Silva, Lorena Rabelo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Miranda Martins, Natália Rezende</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Almeida, Heloísa Gonçalves</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Souza Reis, Vitória</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Maluf, Sarah El Chamy</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Budu, Alexandre</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marinho, Juliane Aparecida</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Abramo, Clarice</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Carmona, Adriana Karaoglanovic</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">da Silva, Marina Goulart</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">da Silva, Gisele Rodrigues</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kemmer, Victor Matheus</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Butera, Anna Paola</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ribeiro-Viana, Renato Márcio</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gazarini, Marcos Leoni</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Júnior, Clébio Soares Nascimento</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Guimarães, Luciana</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">dos Santos, Fabio Vieira</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Castro, Whocely Victor</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Viana, Gustavo Henrique Ribeiro</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Brito, Cristiana Ferreira Alves</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Pilla Varotti, Fernando</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Heyden, Mariano L.M. ELSEVIER</subfield><subfield code="t">The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms</subfield><subfield code="d">2022</subfield><subfield code="d">official journal of the European Federation for Pharmaceutical Sciences</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV009954198</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:138</subfield><subfield code="g">year:2019</subfield><subfield code="g">day:1</subfield><subfield code="g">month:10</subfield><subfield code="g">pages:0</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejps.2019.105015</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">85.05</subfield><subfield code="j">Betriebssoziologie</subfield><subfield code="j">Betriebspsychologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">85.06</subfield><subfield code="j">Unternehmensführung</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">89.52</subfield><subfield code="j">Politische Psychologie</subfield><subfield code="j">Politische Soziologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">138</subfield><subfield code="j">2019</subfield><subfield code="b">1</subfield><subfield code="c">1001</subfield><subfield code="h">0</subfield></datafield></record></collection>
|
| author |
Guimarães, Daniel Silqueira Martins |
| spellingShingle |
Guimarães, Daniel Silqueira Martins ddc 300 bkl 85.05 bkl 85.06 bkl 89.52 Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| authorStr |
Guimarães, Daniel Silqueira Martins |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV009954198 |
| format |
electronic Article |
| dewey-ones |
300 - Social sciences 330 - Economics 360 - Social problems & services; associations |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| topic |
ddc 300 bkl 85.05 bkl 85.06 bkl 89.52 |
| topic_unstemmed |
ddc 300 bkl 85.05 bkl 85.06 bkl 89.52 |
| topic_browse |
ddc 300 bkl 85.05 bkl 85.06 bkl 89.52 |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
s l l s d slls sllsd n s b d nsb nsbd l r s lr lrs m m n r d mmnr mmnrd a h g d ahg ahgd s r v d srv srvd s e c m sec secm a b ab j a m ja jam c a ca a k c ak akc s m g d smg smgd s g r d sgr sgrd v m k vm vmk a p b ap apb r m r v rmr rmrv m l g ml mlg c s n j csn csnj l g lg s f v d sfv sfvd c w v d cwv cwvd g h r v ghr ghrv b c f a d bcfa bcfad p v f d pvf pvfd |
| hierarchy_parent_title |
The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |
| hierarchy_parent_id |
ELV009954198 |
| dewey-tens |
300 - Social sciences, sociology & anthropology 330 - Economics 360 - Social problems & social services |
| hierarchy_top_title |
The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV009954198 |
| title |
Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| ctrlnum |
(DE-627)ELV047685891 (ELSEVIER)S0928-0987(19)30279-9 |
| title_full |
Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| author_sort |
Guimarães, Daniel Silqueira Martins |
| journal |
The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |
| journalStr |
The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
300 - Social sciences |
| recordtype |
marc |
| publishDateSort |
2019 |
| contenttype_str_mv |
zzz |
| container_start_page |
0 |
| author_browse |
Guimarães, Daniel Silqueira Martins |
| container_volume |
138 |
| class |
300 330 360 VZ 85.05 bkl 85.06 bkl 89.52 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
Guimarães, Daniel Silqueira Martins |
| doi_str_mv |
10.1016/j.ejps.2019.105015 |
| dewey-full |
300 330 360 |
| title_sort |
improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: mode of action, mutagenicity profile, and caco-2 cell-based permeability |
| title_auth |
Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| abstract |
The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. |
| abstractGer |
The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. |
| abstract_unstemmed |
The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound. |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U |
| title_short |
Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability |
| url |
https://doi.org/10.1016/j.ejps.2019.105015 |
| remote_bool |
true |
| author2 |
de Sousa Luz, Letícia Silveira do Nascimento, Sara Batista Silva, Lorena Rabelo de Miranda Martins, Natália Rezende de Almeida, Heloísa Gonçalves de Souza Reis, Vitória Maluf, Sarah El Chamy Budu, Alexandre Marinho, Juliane Aparecida Abramo, Clarice Carmona, Adriana Karaoglanovic da Silva, Marina Goulart da Silva, Gisele Rodrigues Kemmer, Victor Matheus Butera, Anna Paola Ribeiro-Viana, Renato Márcio Gazarini, Marcos Leoni Júnior, Clébio Soares Nascimento Guimarães, Luciana dos Santos, Fabio Vieira de Castro, Whocely Victor Viana, Gustavo Henrique Ribeiro de Brito, Cristiana Ferreira Alves de Pilla Varotti, Fernando |
| author2Str |
de Sousa Luz, Letícia Silveira do Nascimento, Sara Batista Silva, Lorena Rabelo de Miranda Martins, Natália Rezende de Almeida, Heloísa Gonçalves de Souza Reis, Vitória Maluf, Sarah El Chamy Budu, Alexandre Marinho, Juliane Aparecida Abramo, Clarice Carmona, Adriana Karaoglanovic da Silva, Marina Goulart da Silva, Gisele Rodrigues Kemmer, Victor Matheus Butera, Anna Paola Ribeiro-Viana, Renato Márcio Gazarini, Marcos Leoni Júnior, Clébio Soares Nascimento Guimarães, Luciana dos Santos, Fabio Vieira de Castro, Whocely Victor Viana, Gustavo Henrique Ribeiro de Brito, Cristiana Ferreira Alves de Pilla Varotti, Fernando |
| ppnlink |
ELV009954198 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth |
| doi_str |
10.1016/j.ejps.2019.105015 |
| up_date |
2024-07-06T16:49:35.231Z |
| _version_ |
1803849118761615360 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV047685891</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626020201.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">191022s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejps.2019.105015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000725.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV047685891</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0928-0987(19)30279-9</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">300</subfield><subfield code="a">330</subfield><subfield code="a">360</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">85.05</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">85.06</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">89.52</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Guimarães, Daniel Silqueira Martins</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019transfer abstract</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Sousa Luz, Letícia Silveira</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">do Nascimento, Sara Batista</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Silva, Lorena Rabelo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Miranda Martins, Natália Rezende</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Almeida, Heloísa Gonçalves</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Souza Reis, Vitória</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Maluf, Sarah El Chamy</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Budu, Alexandre</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marinho, Juliane Aparecida</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Abramo, Clarice</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Carmona, Adriana Karaoglanovic</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">da Silva, Marina Goulart</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">da Silva, Gisele Rodrigues</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kemmer, Victor Matheus</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Butera, Anna Paola</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ribeiro-Viana, Renato Márcio</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gazarini, Marcos Leoni</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Júnior, Clébio Soares Nascimento</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Guimarães, Luciana</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">dos Santos, Fabio Vieira</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Castro, Whocely Victor</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Viana, Gustavo Henrique Ribeiro</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Brito, Cristiana Ferreira Alves</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">de Pilla Varotti, Fernando</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Heyden, Mariano L.M. ELSEVIER</subfield><subfield code="t">The face of wrongdoing? An expectancy violations perspective on CEO facial characteristics and media coverage of misconducting firms</subfield><subfield code="d">2022</subfield><subfield code="d">official journal of the European Federation for Pharmaceutical Sciences</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV009954198</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:138</subfield><subfield code="g">year:2019</subfield><subfield code="g">day:1</subfield><subfield code="g">month:10</subfield><subfield code="g">pages:0</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejps.2019.105015</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">85.05</subfield><subfield code="j">Betriebssoziologie</subfield><subfield code="j">Betriebspsychologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">85.06</subfield><subfield code="j">Unternehmensführung</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">89.52</subfield><subfield code="j">Politische Psychologie</subfield><subfield code="j">Politische Soziologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">138</subfield><subfield code="j">2019</subfield><subfield code="b">1</subfield><subfield code="c">1001</subfield><subfield code="h">0</subfield></datafield></record></collection>
|
| score |
7.3993683 |