Synthesis and cytotoxic evaluation of quinazolin-4(3H)-one derivatives bearing thiocarbamate, thiourea or N-methyldithiocarbamate side chains.

We have previously found that the dithiocarbamate derivatives of quinazolin-4(3H)-one could act as cytotoxic agents against a panel of human tumor cell lines. To investigate the contribution of dithiocarbamate moiety to the cytotoxic activity, three series of novel quinazolin-4(3H)-one derivatives bearing thiocarbamate, thiourea or Nmethyldithiocarbamate side chains were synthesized and tested for their cytotoxic activity against human cancer cell lines A549, MCF-7, HeLa, HT29 and HCT-116 by MTT assay. The results showed that transformation of the dithiocarbamate moiety in lead compound I to thiocarbamate or thiourea led to a decrease or loss of cytotoxic activity.

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 IC(50) values of 5.44, 7.

Synthesis and cytotoxicity screening of piperazine-1-carbodithioate derivatives of 2-substituted quinazolin-4(3H)-ones.

A new series of piperazine-1-carbodithioate derivatives of 2-substituted quinazolin-4(3H)-ones were synthesized via a five-steps procedure starting from 2-amino-5-methylbenzoic acid. The cytotoxicity of the resulting compounds against A-549 (human lung cancer), HCT-8 (human colon cancer), HepG2 (human liver cancer), and K562 (human myelogenous leukaemia) cell lines was determined by the MTT assay. Preliminary screening results of these compounds are reported.