Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.