Palladium-catalyzed synthesis of novel pyrido[3,4-d]pyridazin-1(2H)-ones as promising α-glucosidase, α-amylase and EGFR inhibitors along with molecular docking

A novel route has been established for the synthesis of novel pyrido[3,4-d]pyridazin-1(2H)-one derivative. Synthesis of intermediate 4-methyl-7-(piperazin-1-yl)pyrido[3,4-d]pyridazin-1(2H)-one carried out in the presence of Pd(PPh3)(2)Cl-2 catalyst. Ten novel derivatives were synthesized, isolated, and characterized by various spectroscopic techniques. All synthesized molecules were screened for in silico parameters and evaluated for alpha-glucosidase and alpha-amylase inhibitory assay. Furthermore, all synthesized molecules were screened for anticancer activity against human lung cell line (A549), human melanoma cell line (A375) and breast cancer (MCF-7) cell lines and their cytotoxic effects were compared. Among the compounds, 8i showed higher inhibition than standard acarbose in the antidiabetic assay. In addition, 8 g exhibited more potency than positive control doxorubicin on lung, breast, and melanoma cancer cell lines. A molecular docking study was carried out on 1RPK and 4HJO as Epidermal growth factor receptor (EGFR) proteins.