Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors.

Journal Article (Journal Article)

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-methoxy-N-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 μM respectively, which is slightly weaker than that of lead compound PF-74 (EC50 = 0.42 μM). 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.

Full Text

Duke Authors

Cited Authors

  • Li, J; Jiang, X; Dick, A; Prakash Sharma, P; Chen, C-H; Rathi, B; Kang, D; Wang, Z; Ji, X; Lee, K-H; Cocklin, S; Liu, X; Zhan, P

Published Date

  • October 15, 2021

Published In

Volume / Issue

  • 48 /

Start / End Page

  • 116414 -

PubMed ID

  • 34562701

Pubmed Central ID

  • PMC9127657

Electronic International Standard Serial Number (EISSN)

  • 1464-3391

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2021.116414


  • eng

Conference Location

  • England