Pharmacophore modeling and 3D QSAR studies of aryl amine derivatives as potential lumazine synthase inhibitors

Design and discovery of novel antifungal compounds is the need of time, more than ever before due to the unavailability of effective antifungal therapy to treat resistant fungal infections. Due to morphological and functional similarities of fungi both with plant cell and human cell, the search for effective targets leading to specificity of antifungal drug action becomes all that more difficult. For the design of novel antifungal agents, it is necessary to comprehend the life cycle, morphology, metabolic pathways, etc. of fungi scientifically and systematically to identify critical targets for antifungal drug design. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for the design of newer antifungal agents. The pharmacophore modeling and 3D QSAR studies were carried out on 32 N-substituted aryl amine derivatives as fungal lumazine synthase inhibitors. The selected model of 3D QSAR showed positive correlation of electronic descriptors with antifungal activity while steric and hydrophobic descriptors showed negative correlation with antifungal activity. The resulting model exhibited good q(2) and r(2) values up to 0.9109 and 0.845 respectively. (C) 2012 Production and hosting by Elsevier B. V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license.