3D Pharmacophore Model for Insect Repellent Activity and Discovery of New Repellent Candidates

Abstract

To better understand the mechanism of insect repellency and to identify new repellent candidates, we performed a three-dimensional quantitative structure-activity (QSAR) study and developed a pharmacophore model for potent repellent activity from a set of eleven known diverse insect repellent compounds by using the CATALYST 3D-QSAR methodology. The protection time for repellent activity of the compounds was taken from an earlier published study. The pharmacophore was found to have three hydrophobic sites (two aliphatic and one aromatic) and a hydrogen-bond acceptor site in specific locations in the three dimensional geometry of the molecules that are critical for potent repellent activity. The pharmacophore showed an excellent correlation (correlation = 0.9) between the experimental protection time afforded by the compounds in the training set and their predicted protection time. The validity of the pharmacophore model goes beyond the list in the training set and is found to map well on a variety of other insect repellents. By mapping this model on one of the more potent analogue we have generated a three-dimensional shape based template which allowed a search of our in-house compound database and discover four new potential insect repellent candidates.