Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents.

Abstract

Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC50 value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.

• Authors: Wenzhi Wang, Lei Lei, Zhi Liu, Hongbo Wang, Qingguo Meng
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 5 (Mar 01 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 30832266 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Heterocyclic Compounds
• Triterpenes
• Nitrogen
• ursolic acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemical synthesis, chemistry)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Drug Design
• Drug Screening Assays, Antitumor
• HeLa Cells
• Heterocyclic Compounds (administration & dosage, chemical synthesis, chemistry)
• Humans
• Mice
• Molecular Structure
• Neoplasms (drug therapy, pathology)
• Nitrogen (chemistry)
• Structure-Activity Relationship
• Triterpenes (chemistry)
• Xenograft Model Antitumor Assays