Design, synthesis and antiproliferative activity of thiazolo[5,4-d] pyrimidine derivatives through the atom replacement strategy

作者：Li, Zhong-Hua; Liu, Xue-Qi; Geng, Peng-Fei; Zhang, Ji; Ma, Jin-Lian; Wang, Bo; Zhao, Tao-Qian; Zhao, Bing; Zhang, Xin-Hui; Yu, Bin^*; Liu, Hong-Min^*

来源：European Journal of Medicinal Chemistry, 2017, 138: 1034-1041.

DOI：10.1016/j.ejmech.2017.07.039

• Thiazolo[5,4-d]pyrimidine
• Antiproliferative activity
• Apoptosis
• Atom replacement

A series of thiazolo[5,4-d]pyrimidine derivatives were designed through the atom replacement strategy based on biologically validated scaffolds and then evaluated for their antiproliferative activities on cancer cell lines. The structure-activity relationship studies were conducted, leading to the identification of compound 22, which exhibited good antiproliferative activity against HGC-27 with an IC50 value of 1.22 mu M and low toxicity against GES-1 cells. Mechanistic studies showed that compound 22 inhibited the colony formation and migration of HGC-27 as well as induced apoptosis. The western blot experiments proved that compound 22 up-regulated expression of Bax, down-regulated expression levels of Bcl-2 and cleaved caspased-3/9. These findings indicate that compound 22 may serve as a template for designing new agents for the treatment of human gastric cancers. The atom replacement strategy could be viable strategy for designing new anticancer drugs and may find its applications in drug design.

• 出版日期2017-9-29
• 单位郑州大学