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.
Cao
Sheng-Li
SL
Department of Chemistry, Capital Normal University, Beijing 100048, PR China. sl_cao@sohu.com
Wang
Yao
Y
Zhu
Lin
L
Liao
Ji
J
Guo
Yan-Wen
YW
Chen
Lin-Lin
LL
Liu
Hong-Qin
HQ
Xu
Xingzhi
X
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013859:Thiocarbamates