Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents.
J Nat Prod
; 83(9): 2578-2586, 2020 09 25.
Article
em En
| MEDLINE
| ID: mdl-32822186
ABSTRACT
Celastrol, a friedelane-type triterpenoid isolated from the genus Triperygium, possesses antitumor, anti-inflammatory, and immunosuppressive activities. A total of 42 celastrol derivatives (1a-1t, 2a-2l, and 3a-3j) were synthesized and evaluated for their immunosuppressive activities. Compounds 2a-2e showed immunosuppressive effects, with IC50 values ranging from 25 to 83 nM, and weak cytotoxicity (CC50 > 1 µM). Compound 2a, with a selectivity index value 31 times higher than that of celastrol, was selected as a lead compound. Further research showed that 2a exerted its immunosuppressive effects by inducing apoptosis and inhibiting cytokine secretion via Lck- and ZAP-70-mediated signaling pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triterpenos Pentacíclicos
/
Imunossupressores
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2020
Tipo de documento:
Article