Triterpenic azines, a new class of compounds with selective cytotoxicity to leukemia cells CCRF-CEM.

Abstract

AIM:

From betulinic acid (1a), we synthesized 30-oxobetulinic acid (2a) that is highly cytotoxic against many cancer cell lines; however, its generic toxicity is the main obstacle in further development as cytostatic. Methodology & results: From 2a, we prepared a new class of compounds - nonsymmetrical azines and tested their in vitro cytotoxicity. All new azines with a free 28-COOH group (4a-4e) were highly and selectively cytotoxic against the T-lymphoblastic leukemia cell line CCRF-CEM and exhibited dose-dependent inhibition of RNA and DNA synthesis and other cell-cycle alterations, including the M-phase block.

CONCLUSION:

The potential use of azines (4a-4e) in drug development focused on hematological cancers is significantly higher than that of previously studied acids 1a and 2a.

• Authors: Jan Pokorny, Sona Krajcovicova, Marian Hajduch, Martin Holoubek, Sona Gurska, Petr Dzubak, Tereza Volna, Igor Popa, Milan Urban
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 10 Issue 5 Pg. 483-491 (03 01 2018) ISSN: 1756-8927 [Electronic] England
• PMID: 29424548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Hydrazines
• Triterpenes

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Hydrazines (chemical synthesis, chemistry, pharmacology)
• Molecular Conformation
• Structure-Activity Relationship
• Triterpenes (chemical synthesis, chemistry, pharmacology)