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

Abstract

AbstractA 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)2Cl2 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 α‐glucosidase and α‐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.