کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10585760 | 981378 | 2013 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of a novel 5-carbonyl-1H-imidazole-4-carboxamide class of inhibitors of the HIV-1 integrase-LEDGF/p75 interaction
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کلمات کلیدی
IC50cell culture infective doseCCID50CC50EC50HBAHbd50% cytotoxic concentration - 50٪ غلظت سیتوتوکسیک50% inhibitory concentration - 50٪ غلظت مهاری50% effective concentration - 50٪ غلظت موثرHIV-1 integrase - HIV-1 انتگرالLEDGF/p75 - LEDGF / p75Integrase - انتگرالhydrogen bond donor - تامین کننده هیدروژنProtein–protein interaction - تعامل پروتئین-پروتئینAntiviral - ضد ویروسیHIV-1 - ویروس اچ آی وی نوع یکHydrogen bond acceptor - گیرنده پیوند هیدروژن
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Though much progress has been made in the inhibition of HIV-1 integrase catalysis, clinical resistance mutations have limited the promise of long-term drug prescription. Consequently, allosteric inhibition of integrase activity has emerged as a promising approach to antiretroviral discovery and development. Specifically, inhibitors of the interaction between HIV-1 integrase and cellular cofactor LEDGF/p75 have been validated to diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity. Here, we have contributed to the development of novel allosteric integrase inhibitors with a high-throughput AlphaScreen-based random screening approach, with which we have identified novel 5-carbonyl-1H-imidazole-4-carboxamides capable of inhibiting the HIV-1 integrase-LEDGF/p75 interaction in vitro. Following a structure-activity relationship analysis of the initial 1H-imidazole-4,5-dicarbonyl core, we optimized the compound's structure through an industrial database search, and we went further to synthesize a selective and non-cytotoxic panel of inhibitors with enhanced potency.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 19, 1 October 2013, Pages 5963-5972
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 19, 1 October 2013, Pages 5963-5972
نویسندگان
Erik Serrao, Zhong-Liang Xu, Bikash Debnath, Frauke Christ, Zeger Debyser, Ya-Qiu Long, Nouri Neamati,