In silico Molecular Docking and ADME/Tox Study on Benzoxazole Derivatives Against Inosine 5’-Monophosphate Dehydrogenase

Background and Objective: Cryptosporidium parvum (C.parvum) is a microscopic parasite that causes cryptosporidiosis in human.Accessible medications to treat cryptosporidiosis are ineffective and there is yet no immunization against C. parvum.So there is an urgent need to develop a suitable synthetic drug from available databases for suitable targets using computer aided drug designing and quantitative structure activity relationship.Present study was conducted to screen the best compound suitable for binding 5-Monophosphate dehydrogenase (IMPDH) target having optimum binding energy.Materials and Methods: In this regards, 38 benzoxazole derivatives were screened from PubChem compound database and docked with inosine 5-Monophosphate dehydrogenase (IMPDH) of Cryptosporidium parvum using the program AutoDock 4.2 from docked compound.Results: Four best predicted compounds CID 649646, CID 1318080, CID782217, CID1385213 with optimal binding energies -9.48, -9.39, -9.07 and -9.13 kcal moLG 1 were found with IMPDH, respectively.The biological activity of docked compounds in terms of pIC 50 was predicted based on 2D QSAR model built in our previously published work.The docked complex structures were optimized by molecular dynamics simulation with the CHARMM-22 force field using NAMD and evaluated the stability of complex structures by calculating RMSD.In silico ADME/Tox properties of best predicted derivatives of IMPDH were evaluated.Conclusion: The screened compounds showed satisfactory results for oral administration.Compounds have HIA in the range of well absorbed compounds and value in standard range.Skin 2 CaCO P permeability of derivatives showed negative values.Derivatives lightly bind to plasma proteins.The Ames test showed compounds were mutagenic and carcinogenicity showed negative value in mouse and positive value in rat.