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

• Published in: Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 8; no. 2; p. 163
• Main Authors: Cao, Sheng-Li, Xu, Hong, Wang, Yao, Liao, Ji, Zhang, Jing-Jing, Li, Zhong-Feng, Guo, Yan-Wen, Li, Xiao-Rong, Cui, Xue-Mei, Xu, Xingzhi
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2012
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; HT29 Cells; Humans; Molecular Structure; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Quinazolinones - toxicity; Structure-Activity Relationship; Thiocarbamates - chemistry; Thiocarbamates - pharmacology; Thiourea - chemistry; Thiourea - pharmacology
• DOI: 10.2174/157340612800493665

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.