N,N-bis-heteroaryl methylamines: Potent anti-mitotic and highly cytotoxic agents.
Eur J Med Chem
; 168: 176-188, 2019 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-30818177
The synthesis and evaluation of a series of N,N-bis-heterocyclic-methylamines 1 as isoazaerianin analogues are described. It was demonstrated that the replacement of the 3,4,5-trimethoxyphenyl A-ring present in CA-4, isoCA-4 and isoazaerianin by a quinoline or a quinazoline ring is possible and often beneficiary for a high level of cytotoxicity. We have also showed that a carbazole or an indole nucleus are very effective as B-rings in this series, leading to anti-cancer drugs 1 having a sub-nanomolar level of cytotoxicity (1a: IC50â¯=â¯70 pM against HCT116â¯cells). 1a also display a high level of cytotoxicity against four other human cancer cells and inhibited tubulin assembly at a micromolar level. Moreover, at a concentration of 5â¯nM, 1a arrested the cellular cycle in G2/M phase of the cellular cycle and induced apoptosis of HCT116â¯cells. It was also showed that after few hours 1a at a concentration of 10â¯nM totally disrupted endothelial network formation on Matrigel.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citotoxinas
/
Metilaminas
/
Mitosis
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Francia