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

Future Med Chem. 2018 Mar 1;10(5):483-491. doi: 10.4155/fmc-2017-0171. Epub 2018 Feb 9.

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.

Keywords: betulinic acid; cytotoxicity; hydrazone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents, Phytogenic
  • Hydrazines
  • Triterpenes