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

AuthorAli Imanien
AuthorSepehr Soleymanien
AuthorRouhollah Vahabpouren
AuthorZahra Hajimahdien
AuthorAfshin Zarghien
Issued Date2021-07-31en
AbstractA 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 Mg2+ 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 EC50 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 Mg2+ 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.en
DOIhttps://doi.org/10.22037/ijpr.2020.114153.14695en
KeywordDesignen
KeywordSynthesisen
KeywordBenzothiazine-3-carboxamide 1en
Keyword1-dioxideen
KeywordIntegraseen
KeywordAnti-HIVen
PublisherBrieflandsen
TitleDesign, Synthesis, Docking Study and Biological Evaluation of 4-Hydroxy-2<i>H</i>-benzo[<i>e</i>][1,2]thiazine-3-carboxamide 1,1-dioxide Derivatives as Anti-HIV Agentsen
TypeOriginal Articleen

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