Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents

Eur J Med Chem. 2018 Feb 10:145:511-523. doi: 10.1016/j.ejmech.2018.01.006. Epub 2018 Jan 8.

Abstract

A library of 28 analogs of bavachinin including aliphatic and aromatic ethers, epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives have been synthesized and evaluated for cytotoxicity against four different human cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for many analogs compare to bavachinin. Best results were observed for a 1,2,3-triazole analog (17i) with IC50 values 7.72, 16.08, 7.13 and 11.67 μM against lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines respectively. This analog showed three and four fold improvement in cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1). Structure activity relationship (SAR) study for all synthesized analogs was carried out. Further, mechanistic study of the lead molecule (17i) revealed that it inhibits colony formation and in vitro migration of human colon cancer cells (HCT-116). Also, it induced the morphological changes and mediated the apoptotic cell death of HCT-116 cells with perturbance in mitochondrial membrane potential (MMP) and PARP cleavage.

Keywords: Bavachinin; Colony formation; Cytotoxicity; In-vitro migration; MMP; PARP.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Flavonoids / chemical synthesis
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Flavonoids
  • bavachinin