Title of article :
Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth
Author/Authors :
Lixin Qiao، نويسنده , , Lian-Yun Zhao، نويسنده , , Suo-Bao Rong، نويسنده , , Xiong-Wu Wu، نويسنده , , Shaomeng Wang، نويسنده , , Teruhiko Fujii، نويسنده , , Marcelo G. Kazanietz، نويسنده , , Laura Rauser، نويسنده , , Jason Savage، نويسنده , , Bryan L. Roth، نويسنده , , Judith Flippen-Anderson، نويسنده , , Alan P. Kozikowski، نويسنده ,
Abstract :
In view of its role in tumor promotion and signal transduction, protein kinase C (PKC) has proven to be an exciting target for cancer therapy. With the aid of molecular modeling, we rationally designed and stereoselectively synthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was found to exhibit reasonable affinity for PKCδ, with lower affinity for the other isozymes tested. Pyrrolidone Figure 1 and Scheme 1 causes the dose-dependent induction of apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly potentiated by the use of LNCaP cells overexpressing the PKCα or δ isozymes.
