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

Abstract: 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 11.44μM, respectively. Compound 5i was the most potent with an IC50 value of 3.65μM against proliferation of MCF-7 cells, while 5n was the most potent with an IC50 value of 5.09μM 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. [ABSTRACT FROM AUTHOR]