Design, Synthesis and Anticancer Properties of Novel Hydrazino-Fused Pyrimidines

Abstract

The Pyrimidine system has received great attention and a vital component of genetic material emerged has fundamental source to fight against cancer. The pyrazolo(1,5-a) pyrimidines (5a-5j) were designed based on the structural features of antitumor antimetabolites, synthesized and chemical structures were confirmed using spectroscopic methods such as IR, 1H NMR, 13C NMR, Mass Spectral and elemental analysis. The cytotoxic activity was evaluated by DPPH free radical scavenging assay against standard ascorbic acid and MTT assay against MCF-7, HepG-2, and imatinib as standard. The DPPH assay indicated 5b, 5c, 5e, 5h and 5j were efficient antioxidants, while the MTT assay discloses potent cytotoxicity of 5b, 5d against MCF-7 with 16.61, 19.67µg/ml and 5c, 5h against HepG-2 with 14.32 and 19.24µg/ml compared to 5-FU. The ligands 5c and 5h demonstrated promising towards tyrosine kinase and cyclin dependent kinase 2, respectively and the bonding energy is similar as doxorubicin. Concluding that the compounds had reasonable cytotoxic potential and good association observed between in vitro and in silico studies.