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

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

[学科分类] 工程和技术（综合）

[关键词] Valdecoxib;DFT;Lipophilicity;NBO