Synthesis of novel heterocyclic oleanolic acid derivatives with improved antiproliferative activity in solid tumor cells.

Abstract

A series of new oleanane imidazole carbamates, N-acylimidazoles or N-alkylimidazoles were synthesized, characterized and evaluated for their antiproliferative activity in AsPC-1 pancreatic cancer cells. Structure-activity relationship analysis revealed that the N-alkylimidazole 27 was the most active compound with apoptosis induction abilities correlated with upregulation of NOXA and downregulation of Bcl-xL. The antiproliferative activity of compound 27 was further tested in more solid tumor cell lines with IC(50) values lower than 1 μM.

• Authors: Ana S Leal, Rui Wang, Jorge A R Salvador, Yongkui Jing
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 11 Issue 10 Pg. 1726-38 (Feb 13 2013) ISSN: 1477-0539 [Electronic] England
• PMID: 23381885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Heterocyclic Compounds
• Oleanolic Acid

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Molecular Conformation
• Oleanolic Acid (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured