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Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents

A novel series of benzothiazine-3-carboxamide 1,1-dioxide derivatives by modifying the piroxicam scaffold was designed, synthesized, and evaluated as anti-HIV agents. The 1,2-benzothiazine-3-carboxamide 1,1-dioxide scaffold consists of hydroxy and carboxamide groups as a chelating motif to form an i...

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Autores principales: Imani, Ali, Soleymani, Sepehr, Vahabpour, Rouhollah, Hajimahdi, Zahra, Zarghi, Afshin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653674/
https://www.ncbi.nlm.nih.gov/pubmed/34903964
http://dx.doi.org/10.22037/ijpr.2020.114153.14695
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author Imani, Ali
Soleymani, Sepehr
Vahabpour, Rouhollah
Hajimahdi, Zahra
Zarghi, Afshin
author_facet Imani, Ali
Soleymani, Sepehr
Vahabpour, Rouhollah
Hajimahdi, Zahra
Zarghi, Afshin
author_sort Imani, Ali
collection PubMed
description A novel series of benzothiazine-3-carboxamide 1,1-dioxide derivatives by modifying the piroxicam scaffold was designed, synthesized, and evaluated as anti-HIV agents. The 1,2-benzothiazine-3-carboxamide 1,1-dioxide scaffold consists of hydroxy and carboxamide groups as a chelating motif to form an interaction with Mg(2+) ions within the integrase active site as a target. Most of the compounds displayed encouraging anti-HIV activity in a cell-based assay. Among them, compounds 13d, 13l and 13m were the most potent with EC(50) values ranging from 20-25 µM and SI > 26. Docking study of compounds in integrase active site proposed that the mechanism of action of compounds might be through Mg(2+) chelation within integrase active site. The lack of severe cytotoxicity and favorable anti-HIV activity of benzothiazine-3-carboxamide 1,1-dioxide derivatives support further modifications to improve the potency.
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spelling pubmed-86536742021-12-12 Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents Imani, Ali Soleymani, Sepehr Vahabpour, Rouhollah Hajimahdi, Zahra Zarghi, Afshin Iran J Pharm Res Original Article A novel series of benzothiazine-3-carboxamide 1,1-dioxide derivatives by modifying the piroxicam scaffold was designed, synthesized, and evaluated as anti-HIV agents. The 1,2-benzothiazine-3-carboxamide 1,1-dioxide scaffold consists of hydroxy and carboxamide groups as a chelating motif to form an interaction with Mg(2+) ions within the integrase active site as a target. Most of the compounds displayed encouraging anti-HIV activity in a cell-based assay. Among them, compounds 13d, 13l and 13m were the most potent with EC(50) values ranging from 20-25 µM and SI > 26. Docking study of compounds in integrase active site proposed that the mechanism of action of compounds might be through Mg(2+) chelation within integrase active site. The lack of severe cytotoxicity and favorable anti-HIV activity of benzothiazine-3-carboxamide 1,1-dioxide derivatives support further modifications to improve the potency. Shaheed Beheshti University of Medical Sciences 2021 /pmc/articles/PMC8653674/ /pubmed/34903964 http://dx.doi.org/10.22037/ijpr.2020.114153.14695 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Imani, Ali
Soleymani, Sepehr
Vahabpour, Rouhollah
Hajimahdi, Zahra
Zarghi, Afshin
Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title_full Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title_fullStr Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title_full_unstemmed Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title_short Design, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agents
title_sort design, synthesis, docking study and biological evaluation of 4-hydroxy-2h-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide derivatives as anti-hiv agents
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653674/
https://www.ncbi.nlm.nih.gov/pubmed/34903964
http://dx.doi.org/10.22037/ijpr.2020.114153.14695
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