Efficient Synthesis and Biological Evaluation of 2,4-Diaminothieno[2,3-d]pyrimidine Derivative

Cancer is a main reason for human morbidity and mortality globally. Screening and identifying new anticancer chemical substances is considered as a valid treatment for carcinoma. In our study on synthesis and search towards the development of potential anticancer agents, a series of thieno[2,3-d]pyrimidine derivatives were prepared from the functionalized iminophosphorane via aza-Wittig reaction. Their structures were confirmed by (HNMR)-H-1, (CNMR)-C-13, MS and elementalanalysis. The invitro antitumor activities of compounds were analyzed with CCK8 standard method. It revealed these thieno[2,3-d]pyrimidine derivatives were exhibited cytotoxicity against HepG2, HEp-2, and MCF-7cell lines. The most potent compounds, 5h and 5j, were efficacious against HEp-2 cells with IC50 1.8mol/L and 0.8mol/L, respectively. Meanwhile, 5a, 5d and 5h showed broad spectrum of cytotoxicity for HepG2, Hep2 and MCF-7 three different cell lines with IC50 range of 1.8-87.5mol/L. Furthermore, we demonstrated that cytotoxicity of 5j was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent.