Synthesis and antitumor activity evaluation of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at C4-position

• Published in: Bioorganic & medicinal chemistry letters 2016-10, Vol.26 (19), p.4666-4670
• Main Authors: Zhang, Ying, Yang, Chao-Rui, Tang, Xue, Cao, Sheng-Li, Ren, Ting-Ting, Gao, Man, Liao, Ji, Xu, Xingzhi
• Format: Article
• Language: English
• Subjects: Animals; Antiproliferative activity; Cell cycle; Cell Line, Tumor; Drug Screening Assays, Antitumor; Heterografts; Humans; Mice; Piperazine-1-carbodithioate; Quinazoline; Quinazolines - chemical synthesis; Quinazolines - chemistry; Quinazolines - pharmacology; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.08.060

4-Quinazolinylpiperazine-1-carbodithioates 8a–q and 9a–i were synthesized. Most of them exhibited promising cytotoxicity, and 8n induced a dose-dependent G0/G1 phase arrest in HCT-116 cells. [Display omitted] A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a–q and 9a–i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action.