Synergistic MgSiO ₃ nanocatalysis for the efficient synthesis of benzo[ d ]oxazol-2-yl phenylisoxazoles: structural elucidation, drug-likeness profiling, and target-oriented biomolecular interactions

A new library of 2-(5-phenylisoxazole-3-yl)benzo[d]oxazole derivatives 3(a–f) was synthesized through a magnesium silicate nanocatalyst-assisted condensation of 2-aminophenol with a series of substituted 5-phenylisoxazole-3-carbaldehydes. The identity of the products was confirmed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Their interaction with calf thymus DNA (CT-DNA) was systematically examined using absorption spectroscopy, viscosity assays, thermal denaturation experiments, and molecular docking simulations. The compounds exhibited binding constants in the 105–106 M−1 range, with 3d showing the strongest affinity (Kb = 1.13 × 106 M−1), consistent with an intercalative binding mode. Docking studies with human DNA (PDB ID: 1G3X) revealed stabilizing hydrogen bonds, π–π stacking, and hydrophobic contacts that corroborated the experimental findings. Electronic properties were further explored through density functional theory calculations at the B3LYP level, which demonstrated that frontier orbital parameters—particularly highest occupied molecular orbital–lowest unoccupied molecular orbital gaps and electrophilicity indices—correlated well with DNA-binding behavior, offering mechanistic insight into the electronic contributions to molecular recognition. In silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling suggested favorable pharmacokinetic attributes and drug-like properties. All derivatives promoted UV-induced cleavage of supercoiled pBR322 DNA, underscoring their potential as photoactive nuclease mimetics. These results identify benzoxazole–isoxazole hybrids as promising scaffolds for DNA-targeted applications in medicinal chemistry and chemical biology.