CoMFA analysis of dual/multiple PPAR activators.
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 PPARalpha/gamma/delta multiple activators. Three individual CoMFA models were first generated, followed by dual and multiple models. Dual PPARalpha/gamma CoMFA model could be developed successfully. However, dual PPARgamma/delta, dual PPARalpha/delta and multiple PPARalpha/gamma/delta CoMFA models could not be very well developed. This follows from the poor correlation observed in the PPARdelta CoMFA model.
Shah
Palak
P
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160062, India.
Mittal
Amit
A
Bharatam
Prasad V
PV
D003198:Computer Simulation; D016208:Databases, Factual; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism
D008024:Ligands; D010069:Oxadiazoles; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D010666:Phenylpropionates; C538759:alpha-isopropoxy phenylpropanoic acid