RESUMEN

A series of novel conjugates of 4-aza-2,3-didehydropodophyllotoxins (11a-w) were synthesized by a straightforward one-step multicomponent synthesis that demonstrated cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). All the twenty three compounds (11a-w) have been examined for the inhibition of tubulin polymerization. Among these compounds, 11a, 11k and 11p exhibited inhibition of polymerization tubulin comparable to podophyllotoxin apart from disruption of microtubule organization within the cells. Flow cytometric analysis showed that these compounds (11a, 11k and 11p) arrested the cell cycle in the G2/M phase of cell cycle leading to caspase-3 dependent apoptotic cell death.

Asunto(s)

Antimitóticos/síntesis química , Antineoplásicos/síntesis química , Podofilotoxina/análogos & derivados , Antimitóticos/química , Antimitóticos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática , Citometría de Flujo , Humanos , Podofilotoxina/síntesis química , Podofilotoxina/química , Podofilotoxina/farmacología , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo