De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors

Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Chander, Subhash [verfasserIn] Ashok, Penta Singh, Anupam Murugesan, Sankaranarayanan

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Tetrahydroisoquinoline HIV-1 RT Docking NNRTI Glide Resistance

Anmerkung:	© Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Chemistry central journal - London : BioMed Central, 2007, 9(2015), 1 vom: 09. Juni
Übergeordnetes Werk:	volume:9 ; year:2015 ; number:1 ; day:09 ; month:06

Links:	Volltext

DOI / URN:	10.1186/s13065-015-0111-6

Katalog-ID:	SPR030132401

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520			\|a Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme.
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allfields	10.1186/s13065-015-0111-6 doi (DE-627)SPR030132401 (SPR)s13065-015-0111-6-e DE-627 ger DE-627 rakwb eng Chander, Subhash verfasserin aut De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213 Ashok, Penta aut Singh, Anupam aut Murugesan, Sankaranarayanan aut Enthalten in Chemistry central journal London : BioMed Central, 2007 9(2015), 1 vom: 09. Juni (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:9 year:2015 number:1 day:09 month:06 https://dx.doi.org/10.1186/s13065-015-0111-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015 1 09 06
spelling	10.1186/s13065-015-0111-6 doi (DE-627)SPR030132401 (SPR)s13065-015-0111-6-e DE-627 ger DE-627 rakwb eng Chander, Subhash verfasserin aut De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213 Ashok, Penta aut Singh, Anupam aut Murugesan, Sankaranarayanan aut Enthalten in Chemistry central journal London : BioMed Central, 2007 9(2015), 1 vom: 09. Juni (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:9 year:2015 number:1 day:09 month:06 https://dx.doi.org/10.1186/s13065-015-0111-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015 1 09 06
allfields_unstemmed	10.1186/s13065-015-0111-6 doi (DE-627)SPR030132401 (SPR)s13065-015-0111-6-e DE-627 ger DE-627 rakwb eng Chander, Subhash verfasserin aut De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213 Ashok, Penta aut Singh, Anupam aut Murugesan, Sankaranarayanan aut Enthalten in Chemistry central journal London : BioMed Central, 2007 9(2015), 1 vom: 09. Juni (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:9 year:2015 number:1 day:09 month:06 https://dx.doi.org/10.1186/s13065-015-0111-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015 1 09 06
allfieldsGer	10.1186/s13065-015-0111-6 doi (DE-627)SPR030132401 (SPR)s13065-015-0111-6-e DE-627 ger DE-627 rakwb eng Chander, Subhash verfasserin aut De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213 Ashok, Penta aut Singh, Anupam aut Murugesan, Sankaranarayanan aut Enthalten in Chemistry central journal London : BioMed Central, 2007 9(2015), 1 vom: 09. Juni (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:9 year:2015 number:1 day:09 month:06 https://dx.doi.org/10.1186/s13065-015-0111-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015 1 09 06
allfieldsSound	10.1186/s13065-015-0111-6 doi (DE-627)SPR030132401 (SPR)s13065-015-0111-6-e DE-627 ger DE-627 rakwb eng Chander, Subhash verfasserin aut De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213 Ashok, Penta aut Singh, Anupam aut Murugesan, Sankaranarayanan aut Enthalten in Chemistry central journal London : BioMed Central, 2007 9(2015), 1 vom: 09. Juni (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:9 year:2015 number:1 day:09 month:06 https://dx.doi.org/10.1186/s13065-015-0111-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015 1 09 06
language	English
source	Enthalten in Chemistry central journal 9(2015), 1 vom: 09. Juni volume:9 year:2015 number:1 day:09 month:06
sourceStr	Enthalten in Chemistry central journal 9(2015), 1 vom: 09. Juni volume:9 year:2015 number:1 day:09 month:06
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Tetrahydroisoquinoline HIV-1 RT Docking NNRTI Glide Resistance
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authorswithroles_txt_mv	Chander, Subhash @@aut@@ Ashok, Penta @@aut@@ Singh, Anupam @@aut@@ Murugesan, Sankaranarayanan @@aut@@
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Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. 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author	Chander, Subhash
spellingShingle	Chander, Subhash misc Tetrahydroisoquinoline misc HIV-1 RT misc Docking misc NNRTI misc Glide misc Resistance De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors
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topic_title	De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors Tetrahydroisoquinoline (dpeaa)DE-He213 HIV-1 RT (dpeaa)DE-He213 Docking (dpeaa)DE-He213 NNRTI (dpeaa)DE-He213 Glide (dpeaa)DE-He213 Resistance (dpeaa)DE-He213
topic	misc Tetrahydroisoquinoline misc HIV-1 RT misc Docking misc NNRTI misc Glide misc Resistance
topic_unstemmed	misc Tetrahydroisoquinoline misc HIV-1 RT misc Docking misc NNRTI misc Glide misc Resistance
topic_browse	misc Tetrahydroisoquinoline misc HIV-1 RT misc Docking misc NNRTI misc Glide misc Resistance
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title	De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors
ctrlnum	(DE-627)SPR030132401 (SPR)s13065-015-0111-6-e
title_full	De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors
author_sort	Chander, Subhash
journal	Chemistry central journal
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author_browse	Chander, Subhash Ashok, Penta Singh, Anupam Murugesan, Sankaranarayanan
container_volume	9
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author-letter	Chander, Subhash
doi_str_mv	10.1186/s13065-015-0111-6
title_sort	de-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as hiv-1 reverse transcriptase inhibitors
title_auth	De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors
abstract	Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background Acquired Immune Deficiency Syndrome (AIDS) is the advanced stage of infection caused by Human Immunodeficiency Virus (HIV). HIV/AIDS had a great impact on society, both as an illness and as a source of discrimination. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are structurally diverse group of compounds which binds to Reverse Transcriptase (RT) enzyme of HIV. Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. So, there is an urgent need to discover the NNRTIs, which can be effective against the drug sensitive as well as drug resistant strains of HIV-1 RT. Results Two series of novel thirty, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogues (5a-o) and (8a-o) were designed and synthesized as inhibitor of HIV-1 reverse transcriptase. All the synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectroscopy and evaluated for in-vitro RT inhibitory activity. Among the tested compounds, eighteen compounds exhibited more than 50 % inhibition at tested 100 μM concentration, in which two compounds 8h and 8l showed promising inhibition (74.82 and 72.58 %) respectively. The preliminary structure–activity relationship (SAR) of the test compounds and docking studies of the two significantly active compounds 8h and 8l were performed to examine their putative binding with HIV-RT. Predicted physiochemical parameters of the synthesized compounds were within the acceptable range of drugable properties. Conclusion The results obtained from this investigation revealed that, the synthesized compounds (5a-o) and (8a-o) showed moderate to promising HIV-1 RT inhibition activity. The overall SAR studies can help in identification of further lead as well as in designing of newer potential inhibitor of HIV-1 RT. Graphical AbstractBest docked pose of compound 8h inside the non-nucleoside inhibitory binding pocket of 3MEE enzyme. © Chander et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	1
title_short	De-novo design, synthesis and evaluation of novel 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as HIV-1 reverse transcriptase inhibitors
url	https://dx.doi.org/10.1186/s13065-015-0111-6
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