New PPARgamma ligands based on 2-hydroxy-1,4-naphthoquinone: computer-aided design, synthesis, and receptor-binding studies.
FlexX-based molecular docking study was employed to identify 2-hydroxy-1,4-naphthoquinone as a new 'acidic head group' for the design of a novel series of PPARgamma ligands. To provide the proof of concept, designed molecules were synthesized and evaluated in a standard radioligand-binding assay. Out of eight molecules, four were found to bind to the murine PPARgamma with IC(50) ranging from 0.2 to 56.2 microM as compared to standard pioglitazone, with IC(50) of 0.7 microM.
Sundriyal
Sandeep
S
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Viswanad
Bhoomi
B
Bharathy
Elumalai
E
Ramarao
Poduri
P
Chakraborti
Asit K
AK
Bharatam
Prasad V
PV
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D017076:Computer-Aided Design; D015195:Drug Design; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011485:Protein Binding; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000493:pharmacokinetics
D008024:Ligands; D009285:Naphthoquinones; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone