Files and links (1)
Published, Version of Record (VoR)CC BY-NC V4.0, Open
Journal article
Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors
RSC advances, v 9(50), pp 28961-28986
17 Sep 2019
PMID: 32089839
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The HIV-1 capsid (CA) protein plays crucial roles in both early and late stages of the viral life cycle, which has intrigued researchers to target it to develop anti-HIV drugs. Accordingly, in this research, we report the design, synthesis and biological evaluation of a series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors using the Cu(i)-catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. Among this series of inhibitors, compound II-10c displayed a remarkable anti-HIV activity (EC50 = 2.13 mu M, CC50 > 35.49 mu M). Furthermore, surface plasmon resonance (SPR) binding assays showed that compounds II-10c and PF-74 (lead compound) have similar affinities to HIV-1 CA monomer. Further investigation showed that the weak permeability and water solubility of representative compounds were probably the important factors that restricted their cell-based activity. Preliminary structure-activity relationships (SARs) were inferred based on the activities of these compounds, and their known structure. The most promising new compound was studied with molecular dynamics simulation (MD) to determine the preferred interactions with the drug target. Finally, the activities of members of this series of inhibitors were deeply inspected to find the potential reasons for their anti-HIV-1 activity from various perspectives. This highlights the important factors required to design compounds with improved potency.
Metrics
Details
- Title
- Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors
- Creators
- Xiangyi Jiang - Shandong UniversityGaochan Wu - Shandong UniversityWaleed A. Zalloum - American University of MadabaMegan E. Meuser - Drexel UniversityAlexej Dick - Drexel UniversityLin Sun - Shandong UniversityChin-Ho Chen - Duke UniversityDongwei Kang - Shandong UniversityLanlan Jing - Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R ChinaRuifang Jia - Shandong UniversitySimon Cocklin - Drexel UniversityKuo-Hsiung Lee - Shandong UniversityXinyong Liu - Shandong UniversityPeng Zhan - Shandong University
- Publication Details
- RSC advances, v 9(50), pp 28961-28986
- Publisher
- Royal Soc Chemistry
- Number of pages
- 26
- Grant note
- 2017CXGC1401 / Key Research and Development Project of Shandong Province R01GM125396 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 2017JC006 / Fundamental Research Funds of Shandong University 2016WLJH32 / Young Scholars Program of Shandong University (YSPSDU) 81420108027 / Key Project of NSFC for International Cooperation R01GM125396; T32-MH079785 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 81273354; 81573347 / National Natural Science Foundation of China (NSFC) 2015ZDJS04001 / Major Project of Science and Technology of Shandong Province T32MH079785 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000487104200008
- Scopus ID
- 2-s2.0-85072518068
- Other Identifier
- 991019168630004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary