Synthesis, Cytotoxicity and Antimicrobial Evaluation of New Coumarin-Tagged β-Lactam Triazole Hybrid

Chem Biodivers. 2020 Jan;17(1):e1900462. doi: 10.1002/cbdv.201900462. Epub 2020 Jan 9.

Abstract

A series of coumarin-tagged β-lactam triazole hybrids (10a-10o) were synthesized and tested for their cytotoxic activity against MDA-MB-231 (triple negative breast cancer), MCF-7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK-293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF-7 cancer cell lines with IC50 values of 53.55 and 58.62 μm, respectively. More importantly, compounds 10b and 10d were non-cytotoxic against HEK-293 cell lines. Structure-activity relationship (SAR) studies suggested that the nitro and chloro group at the C-3 position of phenyl ring are favorable for anticancer activity, particularly against MCF-7 cell lines. Furthermore, antimicrobial evaluation of these compounds revealed modest inhibition of examined pathogenic strains with compounds 10c and 10i being the most promising antimicrobial agents against Pseudomonas aeruginosa and Candida albicans, respectively.

Keywords: 1,2,3-triazole; HEK-293; MCF7; MDA-MB-231; biological activity; coumarin; molecular hybridization; synthesis; β-lactam.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Cell Proliferation / drug effects
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Coumarins
  • Triazoles
  • beta-Lactams