Artigo Revisado por pares

Synthesis of triazoloquinazolinone based compounds as tubulin polymerization inhibitors and vascular disrupting agents

2016; Elsevier BV; Volume: 115; Linguagem: Inglês

10.1016/j.ejmech.2016.03.056

ISSN

1768-3254

Autores

Mohsine Driowya, Julien Leclercq, Valérie Verones, Amélie Barczyk, Marie Lecoeur, Nicolas Renault, Nathalie Flouquet, Alina Ghinet, Pascal Berthelot, Nicolas Lebègue,

Tópico(s)

Synthesis and Characterization of Heterocyclic Compounds

Resumo

A series of 1-phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5-ones designed as conformationally restricted CA-4 analogues, were tested for their tubulin polymerization and growth inhibitory activities. The 3-hydroxy-4-methoxy derivatives 11d and 12d are potent inhibitors of tubulin assembly but only the N-methylated amid counterpart 12d possesses potent anticancer activity in a large panel of cancer cell lines. Upon treatment with compound 12d, remarkable cell shape changes as cell migration and tube formation were elicited in HUVECs, consistent with vasculature damaging activity.

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