Rational design, synthesis, and biological evaluation of rigid pyrrolidoneanalogues as potential inhibitors of prostate cancer cell growth

Authors
Qiao, LX Zhao, LY Rong, SB Wu, XW Wang, SM Fujii, T Kazanietz, MG Rauser, L Savage, J Roth, BL Flippen-Anderson, J Kozikowski, AP
Citation
Lx. Qiao et al., Rational design, synthesis, and biological evaluation of rigid pyrrolidoneanalogues as potential inhibitors of prostate cancer cell growth, BIOORG MED, 11(8), 2001, pp. 955-959
Citations number
22
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
8
Year of publication
2001
Pages
955 - 959
Database
ISI
SICI code
0960-894X(20010423)11:8<955:RDSABE>2.0.ZU;2-4
Abstract
In view of its role in tumor promotion and signal transduction, protein kin ase C (PKC) has proven to be an exciting target for cancer therapy. With th e aid of molecular modeling, we rationally designed and stereoselectively s ynthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrr olidone 15 was found to exhibit reasonable affinity for PKC delta, with low er affinity for the other isozymes tested. Pyrrolidone 2 causes the dose-de pendent induction of apoptosis in LNCaP prostate cancer cells. This apoptot ic effect could be markedly potentiated by the use of LNCaP cells overexpre ssing the PKC alpha or delta isozymes. (C) 2001 Elsevier Science Ltd. All r ights reserved.