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. Issue 6 (15th March 2015)

• Record Type: Journal Article
• Authors: Ahmad, Matloob; Aslam, Sana; Rizvi, Syed Umar Farooq; Muddassar, Muhammad; Ashfaq, Usman Ali; Montero, Catherine; Ollinger, Olivia; Detorio, Mervi; Gardiner, John M.; Schinazi, Raymond F.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 6(2015)
• Page Start: 1348
• Page End: 1351
• Publication Date: 2015-03-15
• Subjects: CFNHKSLLNKSRQW-UHFFFAOYSA-N -- KPVBMSHYLHSUBY-UHFFFAOYSA-N -- NQSHGJZYGSBRJG-UHFFFAOYSA-N -- DTGDCKYPNWPOFV-UHFFFAOYSA-N -- SDCRWFYUKNLYRL-UHFFFAOYSA-N -- KLNQZYKCNHHCRQ-UHFFFAOYSA-N -- ZNTFWBZGYGDOHC-UHFFFAOYSA-N -- OBODUFYVMQLYGN-UHFFFAOYSA-N -- JFUIFXNFIHACKB-UHFFFAOYSA-N -- WGNVVZUWMJYQDO-UHFFFAOYSA-N -- ZKDPSSMPYZIXJU-UHFFFAOYSA-N -- IXIQUKFALMYZJP-UHFFFAOYSA-N -- RDJYNVYVPFSVKR-UHFFFAOYSA-N -- SDXZKLLYNMNEIJ-UHFFFAOYSA-N -- QAMZFNDFDZNHIF-UHFFFAOYSA-N -- XGIZUQNWLBCNHQ-UHFFFAOYSA-N -- JILYJVRCHLPYMP-UHFFFAOYSA-N; Pyrazolobenzothiazine -- Anti-HIV activity -- 1, 2-Benzothiazine 1, 1-dioxide -- Reverse transcriptase -- Cytotoxicity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.01.007
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Two series of fifteen N -substituted benzyl/phenyl-2-(3, 4-dimethyl-5, 5-dioxidopyrazolo[4, 3- c ][1, 2]benzothiazin-2(4 H )-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds6a, 6d, 6e, 6g and6i from the series6a –i of benzylamides and7a, 7b, 7c, 7d and7e from the series7a –f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20 μM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that6e, 6g and6i 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.