New phorbol ester derivatives as potent anti-HIV agents. (15th October 2021)

• Record Type: Journal Article
• Authors: Li, Qi-Run; Cheng, Yung-Yi; Zhao, Lei; Huang, Xiao-Lei; Jiang, Xiao-Gang; Cui, Ya-Dong; Morris-Natschke, Susan L.; Goto, Masuo; Chen, Chin-Ho; Lee, Kuo-Hsiung; Chen, Dao-Feng; Zhang, Jian
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 50(2021)
• Publication Date: 2021-10-15
• Subjects: DCM dichloromethane -- DMAP N, N-dimethyl-4-aminopyridine -- EDCI 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride -- PKC protein kinase C -- TPA phorbol ester 12-O-tetradecanoylphorbol-13-acetate; Phorbol esters -- Tigliane diterpenoids -- Anti-HIV activity -- Cytotoxicity -- Non-tumor-promoting; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128319
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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.