Synthesis and in vitro evaluation of 3-(4-nitrophenyl)coumarin derivatives in tumor cell lines

Bioorg Chem. 2015 Feb;58:96-103. doi: 10.1016/j.bioorg.2014.11.009. Epub 2014 Nov 29.


Coumarins are naturally-occurring compounds that have attracted considerable interest due to their numerous biological activities depending on their pattern of substitution on the coumarin molecule. In this present investigation, we synthesized 3-(4-nitrophenyl)coumarin derivatives (9a-e) and evaluated their in vitro cytotoxic effect on human lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cell lines for 48 h using crystal violet dye binding assay. Cytotoxic effects of the most active compound on normal human lung (MRC-9) and breast (MCF-10A) cell lines, cell cycle analysis using flow cytometry and mitochondrial membrane potential (MMP) using Tetramethyl Rhodamine Methyl Ester (TMRM; rhodamine-123) fluorescent dye were also examined. Among the compounds that were evaluated, 9c showed cytotoxic effect (active), caused significant cells arrest (p<0.05) in G0/G1 and S phases of cell cycle and loss of MMP in A459, MDA-MB-231 and PC3 cell lines. Additionally, the cytotoxic effect of 9c was compared to reference drugs (Coumarin and Docetaxel) for comparative study. These results further demonstrate that acetoxy group at C-7 and C-8 positions of 9c are responsible for the observed cytotoxic effect in these cancer cell lines.

Keywords: 3-Arylcoumarin; Anticancer; Cell cycle; Cytotoxicity; Mitochondrial membrane potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Coumarins / chemical synthesis*
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • In Vitro Techniques
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Electrospray Ionization


  • 7,8-diacetoxy-3-(4-nitrophenyl)coumarin
  • Antineoplastic Agents
  • Coumarins