CoMFA analysis of dual/multiple PPAR activators

Abstract

Dual or multiple activators are agents which act at more than one biological target and produce synergistic therapeutic effect. Computational methods can be successfully employed in designing dual activators. ‘Additivity of molecular fields’ concept was recently introduced to help design new dual activators. This concept is employed in this work to explore the scope and limitations of the concept, with the help of reported PPARα/γ/δ multiple activators. Three individual CoMFA models were first generated, followed by dual and multiple models. Dual PPARα/γ CoMFA model could be developed successfully. However, dual PPARγ/δ, dual PPARα/δ and multiple PPARα/γ/δ CoMFA models could not be very well developed. This follows from the poor correlation observed in the PPARδ CoMFA model.