Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs b...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Shekari, Farnaz [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
|---|
| Schlagwörter: |
|---|
| Umfang: |
12 |
|---|
| Übergeordnetes Werk: |
Enthalten in: Mexican student-teachers’ “English” language praxicum: Decolonizing attempts - López-Gopar, Mario E. ELSEVIER, 2022, EJP, New York, NY [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:746 ; year:2015 ; day:5 ; month:01 ; pages:233-244 ; extent:12 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ejphar.2014.10.058 |
|---|
| Katalog-ID: |
ELV023957115 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV023957115 | ||
| 003 | DE-627 | ||
| 005 | 20230625141932.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180603s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejphar.2014.10.058 |2 doi | |
| 028 | 5 | 2 | |a GBVA2015021000007.pica |
| 035 | |a (DE-627)ELV023957115 | ||
| 035 | |a (ELSEVIER)S0014-2999(14)00766-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 610 | |
| 082 | 0 | 4 | |a 610 |q DE-600 |
| 082 | 0 | 4 | |a 370 |q VZ |
| 084 | |a 5,3 |2 ssgn | ||
| 100 | 1 | |a Shekari, Farnaz |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| 264 | 1 | |c 2015transfer abstract | |
| 300 | |a 12 | ||
| 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 Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. | ||
| 520 | |a Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. | ||
| 650 | 7 | |a ABC |2 Elsevier | |
| 650 | 7 | |a P-gp |2 Elsevier | |
| 650 | 7 | |a CCB |2 Elsevier | |
| 650 | 7 | |a MDR |2 Elsevier | |
| 650 | 7 | |a MTT |2 Elsevier | |
| 650 | 7 | |a DHP |2 Elsevier | |
| 650 | 7 | |a Rh123 |2 Elsevier | |
| 700 | 1 | |a Sadeghpour, Hossein |4 oth | |
| 700 | 1 | |a Javidnia, Katayoun |4 oth | |
| 700 | 1 | |a Saso, Luciano |4 oth | |
| 700 | 1 | |a Nazari, Farhad |4 oth | |
| 700 | 1 | |a Firuzi, Omidreza |4 oth | |
| 700 | 1 | |a Miri, Ramin |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a López-Gopar, Mario E. ELSEVIER |t Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |d 2022 |d EJP |g New York, NY [u.a.] |w (DE-627)ELV008405875 |
| 773 | 1 | 8 | |g volume:746 |g year:2015 |g day:5 |g month:01 |g pages:233-244 |g extent:12 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ejphar.2014.10.058 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 951 | |a AR | ||
| 952 | |d 746 |j 2015 |b 5 |c 0105 |h 233-244 |g 12 | ||
| 953 | |2 045F |a 610 | ||
| author_variant |
f s fs |
|---|---|
| matchkey_str |
shekarifarnazsadeghpourhosseinjavidniaka:2015----:yooiadutdurssacrvraatvteonvl4iyrprdn |
| hierarchy_sort_str |
2015transfer abstract |
| publishDate |
2015 |
| allfields |
10.1016/j.ejphar.2014.10.058 doi GBVA2015021000007.pica (DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 370 VZ 5,3 ssgn Shekari, Farnaz verfasserin aut Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier Sadeghpour, Hossein oth Javidnia, Katayoun oth Saso, Luciano oth Nazari, Farhad oth Firuzi, Omidreza oth Miri, Ramin oth Enthalten in Elsevier López-Gopar, Mario E. ELSEVIER Mexican student-teachers’ “English” language praxicum: Decolonizing attempts 2022 EJP New York, NY [u.a.] (DE-627)ELV008405875 volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 https://doi.org/10.1016/j.ejphar.2014.10.058 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U AR 746 2015 5 0105 233-244 12 045F 610 |
| spelling |
10.1016/j.ejphar.2014.10.058 doi GBVA2015021000007.pica (DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 370 VZ 5,3 ssgn Shekari, Farnaz verfasserin aut Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier Sadeghpour, Hossein oth Javidnia, Katayoun oth Saso, Luciano oth Nazari, Farhad oth Firuzi, Omidreza oth Miri, Ramin oth Enthalten in Elsevier López-Gopar, Mario E. ELSEVIER Mexican student-teachers’ “English” language praxicum: Decolonizing attempts 2022 EJP New York, NY [u.a.] (DE-627)ELV008405875 volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 https://doi.org/10.1016/j.ejphar.2014.10.058 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U AR 746 2015 5 0105 233-244 12 045F 610 |
| allfields_unstemmed |
10.1016/j.ejphar.2014.10.058 doi GBVA2015021000007.pica (DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 370 VZ 5,3 ssgn Shekari, Farnaz verfasserin aut Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier Sadeghpour, Hossein oth Javidnia, Katayoun oth Saso, Luciano oth Nazari, Farhad oth Firuzi, Omidreza oth Miri, Ramin oth Enthalten in Elsevier López-Gopar, Mario E. ELSEVIER Mexican student-teachers’ “English” language praxicum: Decolonizing attempts 2022 EJP New York, NY [u.a.] (DE-627)ELV008405875 volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 https://doi.org/10.1016/j.ejphar.2014.10.058 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U AR 746 2015 5 0105 233-244 12 045F 610 |
| allfieldsGer |
10.1016/j.ejphar.2014.10.058 doi GBVA2015021000007.pica (DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 370 VZ 5,3 ssgn Shekari, Farnaz verfasserin aut Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier Sadeghpour, Hossein oth Javidnia, Katayoun oth Saso, Luciano oth Nazari, Farhad oth Firuzi, Omidreza oth Miri, Ramin oth Enthalten in Elsevier López-Gopar, Mario E. ELSEVIER Mexican student-teachers’ “English” language praxicum: Decolonizing attempts 2022 EJP New York, NY [u.a.] (DE-627)ELV008405875 volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 https://doi.org/10.1016/j.ejphar.2014.10.058 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U AR 746 2015 5 0105 233-244 12 045F 610 |
| allfieldsSound |
10.1016/j.ejphar.2014.10.058 doi GBVA2015021000007.pica (DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 DE-627 ger DE-627 rakwb eng 610 610 DE-600 370 VZ 5,3 ssgn Shekari, Farnaz verfasserin aut Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier Sadeghpour, Hossein oth Javidnia, Katayoun oth Saso, Luciano oth Nazari, Farhad oth Firuzi, Omidreza oth Miri, Ramin oth Enthalten in Elsevier López-Gopar, Mario E. ELSEVIER Mexican student-teachers’ “English” language praxicum: Decolonizing attempts 2022 EJP New York, NY [u.a.] (DE-627)ELV008405875 volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 https://doi.org/10.1016/j.ejphar.2014.10.058 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U AR 746 2015 5 0105 233-244 12 045F 610 |
| language |
English |
| source |
Enthalten in Mexican student-teachers’ “English” language praxicum: Decolonizing attempts New York, NY [u.a.] volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 |
| sourceStr |
Enthalten in Mexican student-teachers’ “English” language praxicum: Decolonizing attempts New York, NY [u.a.] volume:746 year:2015 day:5 month:01 pages:233-244 extent:12 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
ABC P-gp CCB MDR MTT DHP Rh123 |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |
| authorswithroles_txt_mv |
Shekari, Farnaz @@aut@@ Sadeghpour, Hossein @@oth@@ Javidnia, Katayoun @@oth@@ Saso, Luciano @@oth@@ Nazari, Farhad @@oth@@ Firuzi, Omidreza @@oth@@ Miri, Ramin @@oth@@ |
| publishDateDaySort_date |
2015-01-05T00:00:00Z |
| hierarchy_top_id |
ELV008405875 |
| dewey-sort |
3610 |
| id |
ELV023957115 |
| 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">ELV023957115</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625141932.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2015 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejphar.2014.10.058</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2015021000007.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV023957115</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0014-2999(14)00766-3</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=" "><subfield code="a">610</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">370</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">5,3</subfield><subfield code="2">ssgn</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Shekari, Farnaz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">12</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">Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">ABC</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">P-gp</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">CCB</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MDR</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MTT</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">DHP</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Rh123</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sadeghpour, Hossein</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Javidnia, Katayoun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Saso, Luciano</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nazari, Farhad</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Firuzi, Omidreza</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Miri, Ramin</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">López-Gopar, Mario E. ELSEVIER</subfield><subfield code="t">Mexican student-teachers’ “English” language praxicum: Decolonizing attempts</subfield><subfield code="d">2022</subfield><subfield code="d">EJP</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV008405875</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:746</subfield><subfield code="g">year:2015</subfield><subfield code="g">day:5</subfield><subfield code="g">month:01</subfield><subfield code="g">pages:233-244</subfield><subfield code="g">extent:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejphar.2014.10.058</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="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">746</subfield><subfield code="j">2015</subfield><subfield code="b">5</subfield><subfield code="c">0105</subfield><subfield code="h">233-244</subfield><subfield code="g">12</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">610</subfield></datafield></record></collection>
|
| author |
Shekari, Farnaz |
| spellingShingle |
Shekari, Farnaz ddc 610 ddc 370 ssgn 5,3 Elsevier ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| authorStr |
Shekari, Farnaz |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV008405875 |
| format |
electronic Article |
| dewey-ones |
610 - Medicine & health 370 - Education |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
610 610 DE-600 370 VZ 5,3 ssgn Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 Elsevier |
| topic |
ddc 610 ddc 370 ssgn 5,3 Elsevier ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 |
| topic_unstemmed |
ddc 610 ddc 370 ssgn 5,3 Elsevier ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 |
| topic_browse |
ddc 610 ddc 370 ssgn 5,3 Elsevier ABC Elsevier P-gp Elsevier CCB Elsevier MDR Elsevier MTT Elsevier DHP Elsevier Rh123 |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
h s hs k j kj l s ls f n fn o f of r m rm |
| hierarchy_parent_title |
Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |
| hierarchy_parent_id |
ELV008405875 |
| dewey-tens |
610 - Medicine & health 370 - Education |
| hierarchy_top_title |
Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV008405875 |
| title |
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| ctrlnum |
(DE-627)ELV023957115 (ELSEVIER)S0014-2999(14)00766-3 |
| title_full |
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| author_sort |
Shekari, Farnaz |
| journal |
Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |
| journalStr |
Mexican student-teachers’ “English” language praxicum: Decolonizing attempts |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology 300 - Social sciences |
| recordtype |
marc |
| publishDateSort |
2015 |
| contenttype_str_mv |
zzz |
| container_start_page |
233 |
| author_browse |
Shekari, Farnaz |
| container_volume |
746 |
| physical |
12 |
| class |
610 610 DE-600 370 VZ 5,3 ssgn |
| format_se |
Elektronische Aufsätze |
| author-letter |
Shekari, Farnaz |
| doi_str_mv |
10.1016/j.ejphar.2014.10.058 |
| dewey-full |
610 370 |
| title_sort |
cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| title_auth |
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| abstract |
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. |
| abstractGer |
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. |
| abstract_unstemmed |
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents. |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U |
| title_short |
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells |
| url |
https://doi.org/10.1016/j.ejphar.2014.10.058 |
| remote_bool |
true |
| author2 |
Sadeghpour, Hossein Javidnia, Katayoun Saso, Luciano Nazari, Farhad Firuzi, Omidreza Miri, Ramin |
| author2Str |
Sadeghpour, Hossein Javidnia, Katayoun Saso, Luciano Nazari, Farhad Firuzi, Omidreza Miri, Ramin |
| ppnlink |
ELV008405875 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth |
| doi_str |
10.1016/j.ejphar.2014.10.058 |
| up_date |
2024-07-06T20:09:53.066Z |
| _version_ |
1803861720372871168 |
| 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">ELV023957115</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625141932.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2015 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejphar.2014.10.058</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2015021000007.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV023957115</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0014-2999(14)00766-3</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=" "><subfield code="a">610</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">370</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">5,3</subfield><subfield code="2">ssgn</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Shekari, Farnaz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">12</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">Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure–activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin׳s IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5–25µM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77–15.60μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">ABC</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">P-gp</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">CCB</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MDR</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MTT</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">DHP</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Rh123</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sadeghpour, Hossein</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Javidnia, Katayoun</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Saso, Luciano</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nazari, Farhad</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Firuzi, Omidreza</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Miri, Ramin</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">López-Gopar, Mario E. ELSEVIER</subfield><subfield code="t">Mexican student-teachers’ “English” language praxicum: Decolonizing attempts</subfield><subfield code="d">2022</subfield><subfield code="d">EJP</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV008405875</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:746</subfield><subfield code="g">year:2015</subfield><subfield code="g">day:5</subfield><subfield code="g">month:01</subfield><subfield code="g">pages:233-244</subfield><subfield code="g">extent:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejphar.2014.10.058</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="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">746</subfield><subfield code="j">2015</subfield><subfield code="b">5</subfield><subfield code="c">0105</subfield><subfield code="h">233-244</subfield><subfield code="g">12</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">610</subfield></datafield></record></collection>
|
| score |
7.3963633 |