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Journal article
Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors
Bioorganic & medicinal chemistry, v 48, pp 116414-116414
15 Oct 2021
PMID: 34562701
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The HIV-1 Capsid (CA) is considered as a promising target for the development of potent antiviral drugs, due to its multiple roles during the viral life cycle. Herein, we report the design, synthesis, and antiviral activity evaluation of series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors. Among them, 4-methoxyN-methylaniline substituted phenylalanine (II-13c) and indolin-5-amine substituted phenylalanine (V-25i) displayed exceptional anti-HIV-1 activity with the EC50 value of 5.14 and 2.57 mu M respectively, which is slightly weaker than that of lead compound PF-74 (EC50 = 0.42 mu M). Besides, surface plasmon resonance (SPR) binding assay demonstrated II-13c and V-25i prefer to combine with CA hexamer rather than monomer, which is similar to PF-74. Subsequently, molecular dynamics simulation (MD) revealed potential interactions between representative compounds with HIV-1 CA hexamer. Overall, this work laid a solid foundation for further structural optimization to discover novel promising HIV-1 CA inhibitors.
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Details
- Title
- Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors
- Creators
- Jing Li - Shandong UniversityXiangyi Jiang - Shandong UniversityAlexej Dick - Drexel UniversityPrem Prakash Sharma - Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi,Delhi-110007,IndiaChin-Ho Chen - Duke UniversityBrijesh Rathi - Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi,Delhi-110007,IndiaDongwei Kang - Shandong UniversityZhao Wang - Shandong UniversityXiangkai Ji - Shandong UniversityKuo-Hsiung Lee - Univ N Carolina, Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USASimon Cocklin - Drexel UniversityXinyong Liu - Shandong UniversityPeng Zhan - Shandong University
- Publication Details
- Bioorganic & medicinal chemistry, v 48, pp 116414-116414
- Publisher
- Elsevier
- Number of pages
- 15
- Grant note
- GXL20200015001 / Foreign cultural and educational experts Project ZR2020JQ31 / Science Foundation for Outstanding Young Scholars of Shandong Province R01GM125396; T32-MH079785; R01AI150491 / Taishan Scholar Program at Shandong Province, NIH 2019JZZY021011 / Shandong 14 Provincial Key research and development project 82173677 / National Natural Science Foundation of China (NSFC) Qilu Young Scholars Program of Shandong University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000705197800004
- Scopus ID
- 2-s2.0-85115432087
- Other Identifier
- 991019168668504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Chemistry, Organic