Discovery of potential lead molecule is a challenging, and complex process which require lots of money, patience, and manpower. Human beings are using natural products, predominantly secondary metabolites, for this purpose since ancient time and they are still working on them as a potent source for drug discovery due to their wide structural diversity. Phenolic phytochemicals such as hydroxytyrosol and tyrosol are natural antioxidant and involved in many biological disease cure. Herein, we have carried out the quantum chemical calculations for conformational analysis, geometry optimization and computation of electronic as well as optical properties of hydroxytyrosol and its analogues (1a-1k) in terms of density functional theory by using Gaussian 09 program suite. The eventual charge transfer within the molecules has been confirmed by the analysis of frontier molecular orbitals. The molecular docking studies of 1a-1k with cyclooxygenase-2 showed the noticeable binding affinity as compared to other nonsteroidal anti-inflammatory drugs viz. aspirin, naproxen and celecoxib. Computation of pharmacokinetics and pharmacological properties confirmed the lead/drug like potential of these screened molecules. Furthermore, the molecular dynamics simulation of best three docked ligands (1f, 1h and 1k)-receptor complex and their binding free energy calculations reveals that these molecules bind in the catalytic cavity of cyclooxygenase-2 and found stable during the 100 ns of simulation. Communicated by Ramaswamy H. Sarma.
Keywords: ADMET; Hydroxytyrosol; MM-PBSA; density functional theory; dynamics simulations.