Synthesis and antiproliferative and apoptosis-inducing activity of novel 3-substituted-3-hydroxy-2-oxindole compounds.

摘要: Anticancer role of oxindole compounds is well documented. Here, we synthesized new derivatives 3-hydroxy-2-oxindole functionalized at position 3 (1a–f) which are expected to have antiproliferative activity in cancer cells. Human prostate cell line (DU145) was treated with the 40-μM concentration for 24, 48, and 72 h. Compounds 1-ethyl-3-hydroxy-1,1′,3,3′-tetrahydro-2H,2′H-3,3′-biindole-2,2′-dione (1d), 5-bromo-1-ethyl-3-hydroxy-1,1′,3,3′-2H,2′H-3,3′-biindole-2,2′-dione (1e), 5-chloro-1-ethyl-3-hydroxy-1,1′,3,3′-tetrahydro-2H,2′H-3,3′-biindole-2,2′-dione (1f) were found significantly reduce DU145 viability 48 72 h whereas no significant changes observed up 24 h. The 1e 1f showed most cytotoxicity effect had a similar on line. They halogen ethyl substitutions positions 5 1, respectively. IC50 compound A375 cells 48 h determined. apoptotic effects cycle progression 1/2 × IC50 (55 μM) investigated by nuclei staining, comet assay, flow cytometry, scanning electron microscopy (SEM). results obtained that this increased percentage tail DNA, occurrence sub-G1 phase, induced G2M arrest apoptosis after exposure 55-μM concentration. SEM images revealed contraction 24 h, condensation, plasma membrane blebbing, formation bodies These observations suggest may be induce