Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers.

Abstract

Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 μM. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 μM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 μM 3c.

• Authors: Sheng-Jie Yang, Ming-Chuan Liu, Hong-Mei Xiang, Qi Zhao, Wei Xue, Song Yang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 102 Pg. 249-55 (Sep 18 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 26280921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Esters
• Pentacyclic Triterpenes
• Triterpenes
• Betulinic Acid

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Esters (chemical synthesis, chemistry, pharmacology)
• Humans
• Mice
• Molecular Structure
• NIH 3T3 Cells
• Pentacyclic Triterpenes
• Structure-Activity Relationship
• Triterpenes (chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured
• Betulinic Acid