title: 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.
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.
authors.affiliation: Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
authors.forename: Matloob
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Department of Chemistry, Government College Women University, Faisalabad, Pakistan.
authors.forename: Sana
authors.initials: S
authors.lastname: Aslam
authors.affiliation: Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Syed Umar Farooq
authors.initials: SU
authors.lastname: Rizvi
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Muddassar
authors.affiliation: Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan.
authors.forename: Usman Ali
authors.initials: UA
authors.lastname: Ashfaq
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine/Veterans Affairs Medical Center, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Montero
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine/Veterans Affairs Medical Center, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Ollinger
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine/Veterans Affairs Medical Center, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Mervi
authors.initials: M
authors.lastname: Detorio
authors.affiliation: School of Chemistry and Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK. Electronic address: gardiner@manchester.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Gardiner
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine/Veterans Affairs Medical Center, 1760 Haygood Drive, Atlanta, GA 30322, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D062105:Molecular Docking Simulation; D019829:Nevirapine / Q000737:chemistry / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014709:Vero Cells
chemical_list: D000081:Acetamides; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: 1,2-Benzothiazine 1,1-dioxide; Anti-HIV activity; Cytotoxicity; Pyrazolobenzothiazine; Reverse transcriptase