Compounds that contain 2-indolinone moieties have been reported to exhibit diverse pharmacological activities. We have recently reported an indoline 2-one containing compound [3-(3-Hydroxy-benzylidene)-6-methoxy-1, 3-dihydro-indol-2-one (OSU 111)] with anti-proliferative, anti-mitotic, apoptosis inducing activities. It displayed potent cytotoxicity with IC50 = 0.5-0.9 μM against human hormone- independent prostate and breast carcinoma cell lines. The inhibition of proliferation correlated with in vitro tubulin polymerization inhibiting activity and cell cycle arrest in G2/M phase of prostate carcinoma cells. The compound was identified to be a colchicine site binder on tubulin. In our continuing research for potent anti-tumor 2-indolinone agents, a series of di- and tri-methoxy benzylidene substituted 1, 3-dihydro-indol-2-one analogs were synthesized. Several tri-methoxy benzylidene substituted analogs exhibited anti-proliferative activity with IC50 values in low nanomolar range against hormone- independent prostate cancer cells. Structures, synthesis, biological activities and modeling studies of the tri-methoxy benzylidene substituted 1, 3-dihydro-indol-2-one analogs will be presented.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]