New phorbol ester derivatives as potent anti-HIV agents.
Anti-HIV activity
Cytotoxicity
Non-tumor-promoting
Phorbol esters
Tigliane diterpenoids
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
received:
04
06
2021
revised:
20
07
2021
accepted:
07
08
2021
pubmed:
18
8
2021
medline:
11
1
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34403728
pii: S0960-894X(21)00546-1
doi: 10.1016/j.bmcl.2021.128319
pii:
doi:
Substances chimiques
Anti-HIV Agents
0
Antineoplastic Agents
0
Phorbol Esters
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128319Informations de copyright
Copyright © 2021. Published by Elsevier Ltd.