Synthesis and cytotoxic activity of N-((2-methyl-4(3H)-quinazolinon-6-yl)methyl)dithiocarbamates

A series of N-((2-methyl-4(3H)-quinazolinon-6-yl)methyl)dithiocarbamates 5a−w were synthesized and evaluated for their cytotoxic activity against five human cancer cell lines. We found that compound 5k inhibited proliferation of A549, MCF-7, HeLa, HT29 and HCT-116 cells with IC50 values of 5.44, 7.15, 12.16, 10.35 and 11.44 μM, respectively. Compound 5i was the most potent with an IC50 value of 3.65 μM against proliferation of MCF-7 cells, while 5n was the most potent with an IC50 value of 5.09 μM against proliferation of A549 cells. Cell cycle analysis showed that both 5i and 5k arrested A549 cells at S and G2/M phases, suggesting that these compounds act through mechanisms different from 5-Fluorouracil, which arrests cells at S phase only.

Compounds 5a–w were synthesized and their cytotoxic activity against five human cancer cell lines together with the effects of three representative compounds on A549 cell cycle progression were examined.Figure optionsDownload as PowerPoint slide