Synthesis and anti-HIV activities of phorbol derivatives.

Autor: Huang X; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China., Tang C; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China., Huang X; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China., Yang Y; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China., Li Q; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China., Ma M; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China., Zhao L; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China., Yang L; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China., Cui Y; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China., Zhang Z; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China. Electronic address: z_zhang@suda.edu.cn., Zheng Y; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China. Electronic address: zhengyt@mail.kiz.ac.cn., Zhang J; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China. Electronic address: jianzhang@suda.edu.cn.
Jazyk: angličtina
Zdroj: Chinese journal of natural medicines [Chin J Nat Med] 2024 Feb; Vol. 22 (2), pp. 146-160.
DOI: 10.1016/S1875-5364(24)60587-X
Abstrakt: 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 , CC 50 /EC 50 11 117.24) and significantly inhibited the formation of syncytium (EC 50 7.0 nmol·L -1 , CC 50 /EC 50 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.)
Databáze: MEDLINE
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