In Silico Molecular Studies and Synthesis of Some Pyridazinone Scaffolds as Anti-proliferative Agents

A series of 6-aryl-2-(imidazol-1-yl/1,2,4-triazol-1-yl)-2-methyl-2,4,5-trihydropyridazin-3-one derivatives (3a-j) were designed, synthesized, and evaluated in different experimental methods to assess their prediction of cell line cytotoxicities, prediction of biological characteristics by Molinspiration, ADMET-based Toxicity prediction with respect to hepatotoxicity, human Ether-a-go-go-Related Gene blocking, acute toxicity (LD50) and Ames toxicity, anatomical therapeutic chemical classification and target prediction, and ADME studies. Molecular docking studies for epidermal growth factor receptor (EGFR) kinase inhibitory activity were calculated as anti-proliferative agent. Following a series of tests, it was discovered that several chemicals had a potential anti-proliferative activity. Furthermore, the synthesized compounds were tested for anti-proliferation activity, and the compounds were shown to be equivalent to Capecitabine, a standard drug. All the tested compounds (3a-j) showed significant chemical and biological parameters as well as EGFR kinase inhibitory activities as anti-proliferative agents.