Synthesis of triterpenoid triazine derivatives from allobetulone and betulonic acid with biological activities.

Abstract

The synthetic transformation and modification of natural products with the aim to improve the biological properties is an area of current interest. The triterpenoids betulin and betulinic acid are very abundant in nature and now are commercially available. In our study, starting from betulin and betulinic acid, we obtained allobetulone and betulonic acid in a few synthetic steps. The ketone function at the A-ring was used as the starting point for the synthesis of a series of 1,2,4-triazine-fused triterpenoids. The alkylation and Liebeskind-Srogl coupling were used for further substitution of 1,2,4-triazines, and the intramolecular hetero Diels-Alder reaction leads to interesting fused thienopyridine derivatives. All new compounds were tested for their cytostatic activities against murine leukemia L1210, human cervix carcinoma HeLa and human lymphoblast CEM tumor cells. The results show that some triterpenoid triazine betulonic acid derivatives have a promising cytostatic activity in vitro and could be used as potential leads for the development of new type of anti-cancer agents. Several compounds were also endowed with anti-HCMV activity in the low micromolar range.

• Authors: Thuc Dinh Ngoc, Nico Moons, Youngju Kim, Wim De Borggraeve, Anastassiya Mashentseva, Graciela Andrei, Robert Snoeck, Jan Balzarini, Wim Dehaen
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 13 Pg. 3292-300 (Jul 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24844757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Triazines
• Triterpenes
• betulonic acid
• Oleanolic Acid

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Viruses (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Microbial Sensitivity Tests
• Molecular Conformation
• Oleanolic Acid (analogs & derivatives, chemistry)
• RNA Viruses (drug effects)
• Structure-Activity Relationship
• Triazines (chemical synthesis, chemistry, pharmacology)
• Triterpenes (chemical synthesis, chemistry, pharmacology)