Design and synthesis of caffeoyl-anilides as portmanteau inhibitors f HIV-1 integrase and CCR5

被引：22

作者：

Bodiwala, Hardik S. ^{[2
]}

Sabde, Sudeep ^{[1
]}

Gupta, Pawan ^{[3
]}

Mukherjee, Ruchira ^{[1
]}

Kumar, Rajender ^{[4
]}

Garg, Prabha ^{[4
]}

Bhutani, Kamlesh Kumar ^{[2
]}

Mitra, Debashis ^{[1
]}

Singh, Inder Pal ^{[2
]}

机构：

[1] NCCS, Pune 411007, Maharashtra, India

[2] NIPER, Dept Nat Prod, Sas Nagar 160062, Punjab, India

[3] NIPER, Ctr Pharmacoinformat, Sas Nagar 160062, Punjab, India

[4] NIPER, Ctr Comp, Sas Nagar 160062, Punjab, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 03期

关键词：

Caffeoyl-anilide; Anti-HIV; Integrase inhibitor; CCR5; inhibitor; Portmanteau inhibitor; SITE BINDING MODES; CHICORIC ACID ANALOGS; ACTIVE-SITE; MOLECULAR-INTERACTIONS; BIOLOGICAL EVALUATION; ANTI-HIV-1; AGENTS; IN-VITRO; DERIVATIVES; ANTAGONISTS; DISCOVERY;

D O I：

10.1016/j.bmc.2010.12.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Designing multi-functional ligands is a recent strategy by which multiple targets can be inhibited by a single entity. A series of caffeoyl-anilide compounds based on structures of various integrase and CCR5 inhibitors have been designed and synthesized as anti-HIV agents in the present study. Most of the compounds exhibited potent anti-HIV activity at micromolar concentration in CEM-GFP CD4+ T cells infected with HIV-1NL4.3 virus. Compound 14 showed a lower EC50 and better TI as compared to AZT. Mechanism based studies suggest that these compounds inhibit either one or in some cases, both the targets. The experimental data and the docking results showed that these compounds are potential inhibitors for both HIV-1 IN and CCR5. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1256 / 1263

页数：8

共 56 条

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