Synthesis, biological evaluation, ADME studies and molecular docking of 1-(3-substituted phenylisoxazol-5-yl) naphthalen-2-ol moiety with VEGFR-2 and Caspase-3 enzymes inhibitors

Abstract

In this investigation, a few isoxazole derivatives have been synthesized from the cyclization of chalcone derivative with hydroxylamine hydrochloride in a basic medium using ultrasonication. The synthesized compound has been confirmed based on 1H NMR, mass spectroscopy and IR analysis. The titled compounds have been screened for their in vivo antimicrobial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. All compounds show excellent activity against Escherichia coli and Staphylococcus aureus bacteria. Each compound has a bioavailability score of 55%, a pain assay score of zero, complies with Lipinski's rule of five, and has high gastrointestinal (GI) absorption. Compounds 3b, 3e, 4b, 4d, and 4e show the best docking scores with VEGFR-2 (PDB IDs: 4ASD, 4ASE) and Caspase-3 (PDB ID: 4QTX), ranging from –8.2 to –9.9 kcal/mol compared to standard curcumin and sorafenib. All the synthesized compounds have excellent docking scores. These compounds may thus be used as lead compounds in studies investigating VEGFR-2 and Caspase-3 inhibitors.