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Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integras...

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Autores principales: Lotfaliei, Mehrnaz, Rezaee, Elham, Hajimahdi, Zahra, Mahboubi Rabbani, Mohammad, Zabihollahi, Rezvan, Aghasadeghi, Mohammad Reza, Tabatabai, Sayyed Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Briefland 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9191218/
https://www.ncbi.nlm.nih.gov/pubmed/35765501
http://dx.doi.org/10.5812/ijpr.123827
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author Lotfaliei, Mehrnaz
Rezaee, Elham
Hajimahdi, Zahra
Mahboubi Rabbani, Mohammad
Zabihollahi, Rezvan
Aghasadeghi, Mohammad Reza
Tabatabai, Sayyed Abbas
author_facet Lotfaliei, Mehrnaz
Rezaee, Elham
Hajimahdi, Zahra
Mahboubi Rabbani, Mohammad
Zabihollahi, Rezvan
Aghasadeghi, Mohammad Reza
Tabatabai, Sayyed Abbas
author_sort Lotfaliei, Mehrnaz
collection PubMed
description HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 μM and an EC50 of 8.4 μM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 μM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents.
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spelling pubmed-91912182022-06-27 Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation Lotfaliei, Mehrnaz Rezaee, Elham Hajimahdi, Zahra Mahboubi Rabbani, Mohammad Zabihollahi, Rezvan Aghasadeghi, Mohammad Reza Tabatabai, Sayyed Abbas Iran J Pharm Res Research Article HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 μM and an EC50 of 8.4 μM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 μM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents. Briefland 2021-12-14 /pmc/articles/PMC9191218/ /pubmed/35765501 http://dx.doi.org/10.5812/ijpr.123827 Text en Copyright © 2022, Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
spellingShingle Research Article
Lotfaliei, Mehrnaz
Rezaee, Elham
Hajimahdi, Zahra
Mahboubi Rabbani, Mohammad
Zabihollahi, Rezvan
Aghasadeghi, Mohammad Reza
Tabatabai, Sayyed Abbas
Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title_full Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title_fullStr Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title_full_unstemmed Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title_short Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation
title_sort novel 2-(diphenylmethylidene) malonic acid derivatives as anti-hiv agents: molecular modeling, synthesis and biological evaluation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9191218/
https://www.ncbi.nlm.nih.gov/pubmed/35765501
http://dx.doi.org/10.5812/ijpr.123827
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