1. Synthesis and anti-HIV activities of phorbol derivatives.
- Author
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Huang X, Tang C, Huang X, Yang Y, Li Q, Ma M, Zhao L, Yang L, Cui Y, Zhang Z, Zheng Y, and Zhang J
- Subjects
- Molecular Docking Simulation, Phorbol Esters pharmacology, HIV Reverse Transcriptase chemistry, HIV Reverse Transcriptase metabolism, Structure-Activity Relationship, Anti-HIV Agents pharmacology, Anti-HIV Agents chemistry, Phorbols chemistry, Phorbols pharmacology
- Abstract
In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC
50 2.9 nmol·L-1 , CC50 /EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1 , CC50 /EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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