Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin2(4H)-yl) acetamides

被引：25

作者：

Ahmad, Matloob ^{[1
]}

Aslam, Sana ^{[2
]}

Rizvi, Syed Umar Farooq ^{[3
]}

Muddassar, Muhammad ^{[4
]}

Ashfaq, Usman Ali ^{[5
]}

Montero, Catherine ^{[6
]}

Ollinger, Olivia ^{[6
]}

Detorio, Mervi ^{[6
]}

Gardiner, John M. ^{[7
,8
]}

Schinazi, Raymond F. ^{[6
]}

机构：

[1] Govt Coll Univ, Dept Chem, Faisalabad 38000, Pakistan

[2] Govt Coll Women Univ, Dept Chem, Faisalabad, Pakistan

[3] Univ Punjab, Inst Chem, Lahore 54590, Pakistan

[4] COMSATS Inst Informat Technol, Dept Biosci, Islamabad, Pakistan

[5] Govt Coll Univ, Dept Bioinformat & Biotechnol, Faisalabad 38000, Pakistan

[6] Emory Univ, Sch Med, Vet Affairs Med Ctr, Ctr AIDS Res,Lab Biochem Pharmacol, Atlanta, GA 30322 USA

[7] Univ Manchester, Sch Chem, Manchester M1 7DN, Lancs, England

[8] Univ Manchester, Manchester Inst Biotechnol, Manchester M1 7DN, Lancs, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 06期

关键词：

Pyrazolobenzothiazine; Anti-HIV activity; 1,2-Benzothiazine 1,1-dioxide; Reverse transcriptase; Cytotoxicity; HIV-1; REVERSE-TRANSCRIPTASE; IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; ANTIBACTERIAL ACTIVITIES; PHARMACOLOGICAL ACTIVITY; DERIVATIVES; TENOFOVIR; EMTRICITABINE; ANTIOXIDANT; EFAVIRENZ;

D O I：

10.1016/j.bmcl.2015.01.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 <20 mu M. 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. (C) 2015 Published by Elsevier Ltd.

引用

页码：1348 / 1351

页数：4

共 33 条

[1] Synthesis and antioxidant studies of novel N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides [J].