Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline

• DOI: 10.1016/j.ejmech.2013.04.017
• Publication Date: 2013-04-17T03:52:01Z
• Authors: Sheng-Li Cao; Ying Han; Chong-Zhen Yuan; Yao Wang; Zhi-Kai Xiahou; Ji Liao; Rui-Ting Gao; Bei-Bei Mao; Bao-Li Zhao; Zhong-Feng Li; Xingzhi Xu
• Keywords: 0301 basic medicine; Dose-Response Relationship, Drug; Molecular Structure; Antineoplastic Agents; HCT116 Cells; Piperazines; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Thiocarbamates; Cell Line, Tumor; MCF-7 Cells; Quinazolines; Humans; HT29 Cells; Cell Proliferation; HeLa Cells

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.