Structure based virtual screening, molecular docking studies and modification of hydantoin nucleus analogues as anticonvulsants

摘要

Neurological disorders such as epilepsy remain a major concern to public health even though considerable therapy efforts aimed for developing effective medicine. The goal of the research is to design, development and identification of potential molecules by analysis and prediction of its interaction pattern with target along its pharmacokinetic parameters. In the present study we have screened and retrieved the Human voltage gated sodium channel target protein entries for epilepsy available in RCSBPDB database and the commercially available drugs as a ligand (such as Phenytoin, Ethotoin, Mephenytoin, fosphenytoin). The drugs have been docked to the above said receptor and the bio affinities values of the docked drugs Phenytoin (-6.50 kcal/mol), Mephenytoin (-6.52 kcal/mol) and Ethotoin (-6.40 kcal / mol) have been calculated using the NOVODOCKER docking module of Inventus v1.1 software. Depending on the bioaffinities values of the drugs several modifications have been carried out on the functional groups to improve the binding scores of the drugs. After screening through HitsGen; hits molecules the analogues of drug molecule were prepared using ChemDraw. Docking studies have been performed and further analysed by pharmacokinetic screening through pharmacopredicta which works through six assays namely CACO, efflux, BBB, FDp, VDSS and finally top 20 modified analogues those being satisfied through all the screening results, have been found to be better than the conventional drugs available and can be taken up for synthesis and in vivo studies.