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New phorbol ester derivatives as potent anti-HIV agents.

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Citation: 

Li, Qi-Run, Yung-Yi Cheng, Lei Zhao, Xiao-Lei Huang, Xiao-Gang Jiang, Ya-Dong Cui, Susan L. Morris-Natschke, et al. “New phorbol ester derivatives as potent anti-HIV agents.” Bioorg Med Chem Lett 50 (October 15, 2021): 128319. https://doi.org/10.1016/j.bmcl.2021.128319.

Published Date: 
Friday, October 15, 2021
Published In: 
Bioorg Med Chem Lett
PMID: 
34403728