Structure-Based Design and Pharmacophore-Based Virtual Screening of Combinatorial Library of Triclosan Analogues Active against Enoyl-Acyl Carrier Protein Reductase of with Favourable ADME Profiles.

Cost-effective therapy of neglected and tropical diseases such as malaria requires everlasting drug discovery efforts due to the rapidly emerging drug resistance of the plasmodium parasite. We have carried out computational design of new inhibitors of the enoyl-acyl carrier protein reductase (ENR) of (ENR) using computer-aided combinatorial and pharmacophore-based molecular design. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) complexation QSAR model was developed for triclosan-based inhibitors (TCL) and a significant correlation was established between the calculated relative Gibbs free energies of complex formation (∆∆Gcom) between ENR and TCL and the observed inhibitory potencies of the enzyme (IC50exp) for a training set of 20 known TCL analogues.

Insight into selectivity of peptidomimetic inhibitors with modified statine core for plasmepsin II of Plasmodium falciparum over human cathepsin D.

Plasmepsin II (PlmII), an aspartic protease expressed in the food vacuole of Plasmodium falciparum (pf), cleaves the hemoglobin of the host during the erythrocytic stage of the parasite life cycle. Various peptidomimetic inhibitors of PlmII reported so far discriminate poorly between the drug target and aspartic proteases of the host organism, e.g.