| Literature DB >> 17449029 |
Shuai Chen1, Xuemei Zhao, Jinzhi Tan, Hong Lu, Zhi Qi, Qiang Huang, Xianzhuo Zeng, Mingjun Zhang, Shibo Jiang, Hualiang Jiang, Long Yu.
Abstract
Cyclophilin A acts as protein folding chaperones and intracellular transports in many cellular processes. Previous studies have shown that cyclophilin A can interact with HIV-1 (human immunodeficiency virus type 1) gag protein and enhance viral infectivity. Many cyclophilin A inhibitors such as cyclosporin A can inhibit HIV-1 replication in vitro. Here, we report a structure-based identification of novel non-peptidic cyclophilin A inhibitors as anti-HIV lead compounds. Following a computer-aided virtual screening and subsequent surface plasmon resonance (SPR) analysis, 12 low molecular weight cyclophilin A ligands were selected for further evaluation of their in vitro inhibition of peptidyl-prolyl cis-trans isomerase (PPIase) activity of cyclophilin A and HIV-1 replication. Five of these compounds (FD5, FD8, FD9, FD10 and FD12) exhibited inhibition against both PPIase activity and HIV-1 infection. These active compounds will be used as leads for structure and activity relationship (SAR) and optimization studies in order to design more effective anti-HIV-1 therapeutics, and as probes for investigating the effect of cyclophilins on HIV-1 replication.Entities:
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Year: 2007 PMID： 17449029 PMCID： PMC3033441 DOI： 10.1016/j.ejphar.2007.03.023
Source DB: PubMed Journal: Eur J Pharmacol ISSN： 0014-2999 Impact factor: 4.432