title: Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline.
abstract: A novel series of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline were synthesized and tested for their antiproliferative activities against five human cancer cell lines including A549 (lung cancer), MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), HT29 and HCT-116 (colorectal cancer). Most of the synthesized compounds showed broad spectrum antiproliferative activity (IC50 1.47-11.83 μM), of which 8f, 8m and 8q were the most active members with IC50 values in the range of 1.58-2.27, 1.84-3.27 and 1.47-4.68 μM against five cancer cell lines examined, respectively. Further investigations revealed that compounds 8f, 8m and 8q exhibited weak inhibition against dihydrofolate reductase and no activity against thymidylate synthase, while induced DNA damage and activated the G2/M checkpoint in HCT-116 cells.
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China. slcao@cnu.edu.cn
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Cao
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Chong-Zhen
authors.initials: CZ
authors.lastname: Yuan
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhi-Kai
authors.initials: ZK
authors.lastname: Xiahou
authors.forename: Ji
authors.initials: J
authors.lastname: Liao
authors.forename: Rui-Ting
authors.initials: RT
authors.lastname: Gao
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Mao
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Zhao
authors.forename: Zhong-Feng
authors.initials: ZF
authors.lastname: Li
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011799:Quinazolines; D013859:Thiocarbamates; C013474:2,4-diaminoquinazoline