Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.
Chem Biodivers
; 20(2): e202200911, 2023 Feb.
Article
en En
| MEDLINE
| ID: mdl-36627123
Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The inâ
vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10â
mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.
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Texto completo:
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Bases de datos:
MEDLINE
Medicinas Tradicionales:
Medicinas_tradicionales_de_asia
/
Medicina_china
Asunto principal:
Bufanólidos
/
Antineoplásicos
Idioma:
En
Revista:
Chem Biodivers
Año:
2023
Tipo del documento:
Article