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. Some N-alkylated analogs of lead compound II preferentially inhibited the proliferation of A549 cells, although their potencies were not improved in comparison with the unalkylated counterparts. The structure-activity relationship obtained in this research will be beneficial for further synthesis and discovery of effective cytotoxic agents.

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, 7.15, 12.16, 10.35 and 11.44 microM, respectively. Compound 5i was the most potent with an IC(50) value of 3.65 microM against proliferation of MCF-7 cells, while 5n was the most potent with an IC(50) value of 5.09 microM 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.

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.

[Study on the ultraviolet spectra of diacetone acrylamide].

Diacetone acrylamide (DAAM) is an important monomer which can be copolymerized with other monomers, so the copolymers with different properties can be obtained. In the present paper, the ultraviolet spectra of diacetone acrylamide solutions in four different solvents (water, acetonitrile, methanol, cyclohexane) were studied, and it was found that there were two strong absorption peaks around 200 nm and 226 nm, respectively. The absorption peak around 200 nm was sensitive to the polarity of the solvent. The absorption shifted to the lower wavelength as the polarity of the solvent was increased, especially in water and acetonitrile. And the adsorption shifted to longer wavelength with the increase in the concentration. However, the other absorption peak at 226 nm remained basically stable when the concentration or the polarity of the solvent was changed. Obviously the absorption at 226 nm is reasonably considered as a characteristic peak of DAAM in the ultraviolet quantitative analysis. And the other absorption peak at 200 nm which is sensitive to the solvent and concentration can be taken to study the interactions between DAAM and solvent molecules. Also, the strength of the adsorption was affected by the polarity of the solvent.