2. Academic Validation
  3. Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

  • Bioorg Med Chem Lett. 2015 Mar 15;25(6):1348-51. doi: 10.1016/j.bmcl.2015.01.007.
Matloob Ahmad 1,  Sana Aslam 2,  Syed Umar Farooq Rizvi 3,  Muhammad Muddassar 4,  Usman Ali Ashfaq 5,  Catherine Montero 6,  Olivia Ollinger 6,  Mervi Detorio 6,  John M Gardiner 7,  Raymond F Schinazi 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
  • 2 Department of Chemistry, Government College Women University, Faisalabad, Pakistan.
  • 3 Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
  • 4 Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan.
  • 5 Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan.
  • 6 Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine/Veterans Affairs Medical Center, 1760 Haygood Drive, Atlanta, GA 30322, USA.
  • 7 School of Chemistry and Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK. Electronic address: gardiner@manchester.ac.uk.
PMID: 25701249 DOI: 10.1016/j.bmcl.2015.01.007
Abstract

Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20μM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and 6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 Reverse Transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral Enzyme.

Keywords

1,2-Benzothiazine 1,1-dioxide; Anti-HIV activity; Cytotoxicity; Pyrazolobenzothiazine; Reverse transcriptase.

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