Synthesis and biological evaluation of novel 3-benzylcoumarin-imidazolium salts

Bioorg Med Chem Lett. 2020 Feb 15;30(4):126896. doi: 10.1016/j.bmcl.2019.126896. Epub 2019 Dec 17.

Abstract

A series of novel 3-benzylcoumarin-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results showed that the existence of 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. Notably, compound 38 was found to be the most potent derivative with IC50 values of 2.04-4.51 μM against five human tumor cell lines, while compound 34 were more selective to SW-480 cell lines with IC50 value 40.0-fold lower than DDP. Mechanism of action studies indicated that compound 38 can cause the G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.

Keywords: 3-Benzylcoumarin; Biological evaluation; Cytotoxic activity; Imidazolium salts; Structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Coumarins / chemistry*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Imidazoles / chemistry*
  • Salts / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coumarins
  • Imidazoles
  • Salts
  • coumarin