Docking and Theoretical Studies of Benzoxazole Derivative with Enhanced NLO and Anti-Hyperlipidemic Activity

Antihyperlipidemic activity refers to a compound’s ability to lower lipid levels, particularly cholesterol and triglycerides, thereby reducing the risk of cardiovascular diseases such as atherosclerosis and coronary artery disease. Benzoxazole derivatives are known for their wide-ranging pharmacological and optoelectronic applications. Computational investigations were performed using DFT and TD-DFT (B3LYP/6-311++G(d,p)) to study optimized geometry, FMO, DOS, MEP, and NLO properties in gas and aqueous phases. Molecular docking (AutoDock Vina, PyRx) was employed against the ACAT enzyme (PDB ID: 1DQ9) to assess bioactivity, with interactions visualized in BIOVIA Discovery Studio. FMO and DOS analyses revealed a narrow HOMO–LUMO gap (4.7185 eV in gas, 4.6643 eV in water), indicating enhanced charge transfer and electronic delocalization in polar media. The MEP map identified active electrophilic and nucleophilic regions, aligning with global reactivity descriptors. TD-DFT results showed π→π* transitions with slight red shifts in aqueous phase, confirming solvent-induced stabilization. Notably, NMBA exhibited an exceptional NLO response with a first-order hyperpolarizability (βtot = 20447.47x10-33 e.s.u.), about 61 times greater than urea, highlighting its strong optical activity. Molecular docking against 1DQ9 protein revealed a high binding affinity (-7.50 kcal/mol) via hydrogen bonding, π–alkyl, and hydrophobic interactions, affirming NMBA’s potential as an effective anti-cholesterol agent. Theoretical and docking results highlight NMBA as a promising multifunctional molecule with superior NLO properties and significant antihyperlipidemic potential, bridging optoelectronic and pharmaceutical applications.