SYNTHESIS, IN-VITRO EVALUATION AND DOCKING STUDIES OF NOVEL 6-AMINO-4-SUBSTITUTED-PYRANO[3,2-D]ISOXAZOLE-5-CARBONITRILE DERIVATIVES AS POTENTIAL ANTI-DIABETIC AND ANTICANCER AGENTS

In this work, we developed an effective protocol for the synthesis of a series of novel 6-amino-4-substituted-pyrano[3,2-d]isoxazole-5-carbonitrile derivatives via one-pot multicomponent reaction of aromatic aldehyde, malononitrile and 3-phenyl-5-isoxazolone in aqueous ethanol using L-proline as a catalyst. The structures of the compounds were confirmed by using analytical and spectroscopic techniques. Further, the obtained compounds were screened for anti-diabetic, cytotoxicity and in silico docking studies. Anti-diabetic activity was done by a-amylase and a-glucosidase assay and cytotoxicity was done by MTT assay. The activity results revealed that most of the analogs exhibited good efficiency when compared with the standards, acarbose and doxorubicin, respectively. The in silico docking study suggested that all the obtained compounds effectively interacted with exo-beta-D-glucosaminidase and P38 MAP kinase proteins. Additionally, the compounds were subjected to in silico ADME studies, which suggested that the compounds met all five requirements with good bioavailability; thus, these compounds can be used as pharmaceutical agents.