title: Synthesis and cytotoxic evaluation of quinazolin-4(3H)-one derivatives bearing thiocarbamate, thiourea or N-methyldithiocarbamate side chains.
abstract: 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.
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, China. sl_cao@sohu.com
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Liao
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Zhong-Feng
authors.initials: ZF
authors.lastname: Li
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Guo
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Li
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Cui
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry* / Q000494:pharmacology; D013890:Thiourea / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D052999:Quinazolinones; D013859:Thiocarbamates; C008435:methyldithiocarbamate; D013890:Thiourea