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Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors

Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thi...

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Autores principales: Ramkumar, Kavya, Yarovenko, Vladimir N., Nikitina, Alexandra S., Zavarzin, Igor V., Krayushkin, Mikhail M., Kovalenko, Leonid V., Esqueda, Adrian, Odde, Srinivas, Neamati, Nouri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264390/
https://www.ncbi.nlm.nih.gov/pubmed/20657419
http://dx.doi.org/10.3390/molecules15063958
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author Ramkumar, Kavya
Yarovenko, Vladimir N.
Nikitina, Alexandra S.
Zavarzin, Igor V.
Krayushkin, Mikhail M.
Kovalenko, Leonid V.
Esqueda, Adrian
Odde, Srinivas
Neamati, Nouri
author_facet Ramkumar, Kavya
Yarovenko, Vladimir N.
Nikitina, Alexandra S.
Zavarzin, Igor V.
Krayushkin, Mikhail M.
Kovalenko, Leonid V.
Esqueda, Adrian
Odde, Srinivas
Neamati, Nouri
author_sort Ramkumar, Kavya
collection PubMed
description Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties.
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spelling pubmed-62643902018-12-04 Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors Ramkumar, Kavya Yarovenko, Vladimir N. Nikitina, Alexandra S. Zavarzin, Igor V. Krayushkin, Mikhail M. Kovalenko, Leonid V. Esqueda, Adrian Odde, Srinivas Neamati, Nouri Molecules Article Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties. MDPI 2010-06-01 /pmc/articles/PMC6264390/ /pubmed/20657419 http://dx.doi.org/10.3390/molecules15063958 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an Open Access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Ramkumar, Kavya
Yarovenko, Vladimir N.
Nikitina, Alexandra S.
Zavarzin, Igor V.
Krayushkin, Mikhail M.
Kovalenko, Leonid V.
Esqueda, Adrian
Odde, Srinivas
Neamati, Nouri
Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title_full Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title_fullStr Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title_full_unstemmed Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title_short Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
title_sort design, synthesis and structure-activity studies of rhodanine derivatives as hiv-1 integrase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264390/
https://www.ncbi.nlm.nih.gov/pubmed/20657419
http://dx.doi.org/10.3390/molecules15063958
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