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

  • Bioorg Med Chem Lett. 2016 Oct 1;26(19):4666-4670. doi: 10.1016/j.bmcl.2016.08.060.
Ying Zhang  1 ,  Chao-Rui Yang  1 ,  Xue Tang  1 ,  Sheng-Li Cao  2 ,  Ting-Ting Ren  1 ,  Man Gao  1 ,  Ji Liao  3 ,  Xingzhi Xu  4
Affiliations
  • 1. Department of Chemistry, Capital Normal University, Beijing 100048, China.
  • 2. Department of Chemistry, Capital Normal University, Beijing 100048, China. Electronic address: [email protected].
  • 3. School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China; Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, China.
  • 4. School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China; Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, China. Electronic address: [email protected].
PMID: 27575478 DOI: 10.1016/j.bmcl.2016.08.060
Abstract

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.

Keywords
Antiproliferative activity; Cell cycle; Piperazine-1-carbodithioate; Quinazoline; Synthesis.