Quantum Chemical Benchmark Study on Valdecoxib, a Potent and Selective Inhibitor of COX-2, and its Hydroxylated Derivative

In this work, quantum chemical calculations were performed on valdecoxib (VLB), a highly selective and potent COX-2 inhibitor, its hydroxylated derivative (1H-VLB), an active metabolite. The geometry optimizations frequency carried out by using density functional theory (DFT)/B3LYP with the 6-311++G (d, p) basis set. To define water phase behaviors, renewed universal SMD solvation model for both molecules. Structural thermodynamic parameters, FT-IR analysis, Mulliken population analysis (MPA), frontier molecular orbital (FMO) natural bond (NBO) electrostatic surface properties investigated in detail. Quantum reactivity identifiers calculated separately vacuum environment order to evaluate bioactivity tendency of mentioned compounds. When VLB 1H-VLB molecules compared based identifiers, it was observed that molecule more active. Moreover, drug-likeness studied predicted means Molinspiration cheminformatics software. Molecular lipophilicity potential (MLP) maps exhibit accumulative lipophilic contributions each atom visualized.