Design and synthesis of some ß-carboline derivatives as multi-target anticancer agents.
Future Med Chem
; 10(24): 2791-2814, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30539666
ABSTRACT
AIM:
Some anticancer ß-carbolines exhibited dual inhibition of topo-I and KSP. METHODOLOGY/RESULTS:
Novel ß-carbolines were synthesized and screened for their anticancer activity according to the NCI protocol. Five dose assays results indicated that compounds 9, 10, 12, 17 and 20 were potent and non selective anticancer agents; the sulfanyltriazole 12 was the most potent. Compounds 10, 12 and 20 showed dual topo-I and KSP inhibition with compound 12 being the most potent. Active compounds elicited Pre-G1 apoptosis and cell cycle arrest at G2/M phase of melanoma MDA-MB-435 cells. Docking results, in silico physicochemical and absorption, distribution, metabolism, excretion (ADME) properties were appropriate.CONCLUSION:
Compounds 10, 12 and 20 are potent apoptosis-inducing multitarget anticancer agents that act via dual inhibition of topo-I and KSP-ATPase.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carbolinas
/
Desenho de Fármacos
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article