In Silico Molecular Design of 4-Benzylidene-6-aryl-2,4,5-trihydropyridazin-3-one Scaffolds as Antiproliferative Targets

Two series of 4-benzylidene-6-(4-methyl-phenyl)-2,4,5-trihydropyridazin-3-ones (2a-e) and 4-benzylidene-6-(4-chlorophenyl)-2,4,5-trihydropyridazin-3-ones (2f-j) were designed to different in silico ex-perimental methods to assess their prediction of biological characteristics by molinspiration, cell line cytotox-icities, ADMET-based toxicity like to hepatotoxicity, hERG (human Ether-à-go-go-Related Gene) blocking, acute toxicity (LD₅₀) and Ames toxicity, anatomical therapeutic chemical (ATC) classification and target pre-dictions. In molecular docking studies, anti-proliferative activity was determined by using epidermal growth factor receptor (EGFR) kinase inhibitory effect of pyridazinone derivatives. Successive assays result showed that some compounds exhibited promising anti-proliferative effect when compared to Ceritinib as a reference drug. All the tested compounds (2a-j) showed significant kinase inhibitory activities.