LAUSR

1-deoxy-D-xylulose-5-phosphate reductoisomerase, catalyzing the rate-limiting step of the isoprenoid synthesis pathway in the malaria parasite, is accredited as a potential drug target. In the present study, a structure based computational approach and biological evaluation were utilized to identify a novel class of compounds as antagonists of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The virtual screening of small molecules was undertaken to identify potential ligands with best binding energies. The stability of selected compounds was explored in molecular dynamics simulation for hundred nanoseconds. The dynamic characteristics of the enzyme-inhibitor complex were investigated by the root mean square deviation and fluctuation plots. Later, two inhibitors (ethyl 2-(2-ethoxy-2-oxoethyl)-2,5-dihydro-1H benzo[b][1,4]diazepine-3-carboxylate and 3,3-dimethyl-11-phenyl-2,3,4,5,10,11-hexahydro-1Hdibenzo[b,e][1,4]diazepin-1-one) exhibited potent antagonistic activity in enzymatic assays with IC50 values in the micromolar range. These inhibitors are believed to hamper the captivating step of the synthetic pathway, as a result of which inadequacy of IPP pool will definitely foster the endurance of parasite in the intraerythrocytic stage.