Anti-HIV activity of new pyrazolobenzothiazine 5,5-dioxide-based acetohydrazides

• Type of Material: Article
• Authors: Zunera Khalid, University of Punjab; Sana Aslam, University of Punjab; Matloob Ahmad, Government College University; Munawar A Munawar, University of Punjab; Catherine Montero, Emory University; Mervi Detorio, Emory University; Masood Parvez, University of Calgary; Raymond Schinazi, Emory University
• Language: English
• Date: 2015-10-01
• Publisher: SPRINGER BIRKHAUSER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015, Springer Science Business Media New York
• Final Published Version (URL): http://dx.doi.org/10.1007/s00044-015-1411-z
• Title of Journal or Parent Work: MEDICINAL CHEMISTRY RESEARCH
• Volume: 24
• Issue: 10
• Start Page: 3671
• End Page: 3680
• Grant/Funding Information: This work was also supported in part by NIH grant 2P30-AI-050409 and the Department of Veterans Affairs (RFS), USA. The X-ray coordinate of the compounds has been deposited at Cambridge Crystallographic Data Centre with CCDC numbers 881055.
• Keywords: DERIVATIVES; BIOLOGICAL-ACTIVITY; Science & Technology; Pharmacology & Pharmacy; Cytotoxicity activity; 1,2-Benzothiazine 1,1-dioxides; MOLECULAR DOCKING; INHIBITORS; Anti-HIV-1; Life Sciences & Biomedicine; ANTITUMOR-ACTIVITY; Pyrazolobenzothiazine; Chemistry, Medicinal

Abstract

A series of fifteen new 2-[3-(3-chlorophenyl)-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(2H)-yl]-N′-arylmethyleneacetohydrazides (5a-o) were synthesized and screened for their anti-HIV-1 and cytotoxicity activity. Out of fifteen pyrazolobenzothiazine-based hydrazones, thirteen were found to be active inhibitors of HIV with EC<inf>50</inf> values <20 μM. Moreover, the cytotoxicity results showed that most of the compounds were toxic to PBM, CEM and Vero cell lines. This information could be used for structural modifications to acquire good candidates of HIV drugs.