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

Lixin Qiao, Lian Yun Zhao, Suo Bao Rong, Xiong Wu Wu, Shaomeng Wang, Teruhiko Fujii, Marcelo G. Kazanietz, Laura Rauser, Jason Savage, Bryan L. Roth, Judith Flippen-Anderson, Alan P. Kozikowski

Research output: Contribution to journalArticle

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 2 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.

Original languageEnglish (US)
Pages (from-to)955-959
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume11
Issue number8
DOIs
StatePublished - Apr 23 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Qiao, L., Zhao, L. Y., Rong, S. B., Wu, X. W., Wang, S., Fujii, T., Kazanietz, M. G., Rauser, L., Savage, J., Roth, B. L., Flippen-Anderson, J., & Kozikowski, A. P. (2001). Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth. Bioorganic and Medicinal Chemistry Letters, 11(8), 955-959. https://doi.org/10.1016/S0960-894X(01)00097-X