RESUMEN

A new class of nitrovinyl biphenyl compounds based on the structures of colchicines and allocolchicines were designed, synthesized, and shown to inhibit tubulin polymerization and cause mitotic arrest. A majority of these compounds were found to possess potent anticancer properties, with IC(50) values in the range of 0.05-7 µM, and are equally potent with colchicine in HeLa and MCF-7 cells. Compounds 14 e and 14 f inhibited tubulin assembly by more than 60 %, and flow cytometry studies indicated growth arrest of cells in the G(2)/M phase of the cell cycle in a concentration-dependent manner. Treatment of cells with 14 f resulted in upregulation of cyclin B1 and aurora kinase B mRNA levels, corresponding to growth arrest in the G(2)/M phase of the cell cycle as the mode of action.

Asunto(s)

Antineoplásicos/síntesis química , Compuestos de Bifenilo/química , Colchicina/análogos & derivados , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Aurora Quinasa B , Aurora Quinasas , División Celular , Línea Celular Tumoral , Colchicina/química , Ciclina B1/genética , Ciclina B1/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Fase G2 , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/uso terapéutico , Moduladores de Tubulina/toxicidad