Virtual screening of xanthine oxidase targeted small molecule inhibitors
To discover new lead compounds with high biological activity and specific target for anti-gout drugs,xanthine oxidase(XOD)was used as the target to screen small molecule inhibitors.XOD protein crystal structures were downloaded from PDB database and preprocessed by"Protein preparation wizard"module in Schrödinger 2018.Three pharmacophore were constructed based on the characteristics of XOD active pocket and small molecule ligand action mode.The FDA database and Chemdiv database were screened for molecular docking.The results showed that using febuxostat and XOD docking fraction(-35.790 kJ/mol)as the threshold,206 compounds below the fraction were selected.Through the five principles of drug class and ADMET analysis,it was found that eight compounds had good druggability.The binding free energies of these eight compounds were calculated.Among them,flufenamic acid,roxoxacin,compound 6(CAS:400076-03-1,benzopyrazole compound)and com-pound 7(CAS:866050-17-1,phthalazine compound)acted in a similar way to febuxostat in the positive control group,which can form stable complexes with xanthine oxidase.These results indicated that the four compounds could be the potential xanthine oxidase inhibitors.
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