Title of article :
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
Author/Authors :
Imani, Ali Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences - Tehran, Iran , Soleymani, Sepehr Hepatitis and AIDS department - Pasteur Institute of Iran - Tehran, Iran , Vahabpour, Rouhollah Medical Lab Technology Department - School of Allied Medical Sciences - Shahid Beheshti University of Medical Sciences - Tehran, Iran , Hajimahdi, Zahra Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences - Tehran, Iran , Zarghi, Afshin Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences - Tehran, Iran
Abstract :
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 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.
Keywords :
Anti-HIV , 1-dioxide , Integrase , Benzothiazine-3-carboxamide 1 , Synthesis , Design
Journal title :
Iranian Journal of Pharmaceutical Research(IJPR)
