Bao_2021_ChemMedChem__

Reference

Title : Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors against Pancreatic Lipase - Bao_2021_ChemMedChem__
Author(s) : Bao X , Zhang J , Yang Y , Qian XK , Song PF , Zhao YS , Guan XQ , Zou LW , Wang H
Ref : ChemMedChem , : , 2021
Abstract :

Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones were synthesized and their inhibitory effects against PL were assayed using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones brought us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor against PL (IC50 0.30 microM). In addition, P32 displayed some selectivity over other known serine hydrolase. Molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the Pi-Pi interactions of 2-naphthyl unit (R1) and hydrophobic interactions of phenyl moiety (R3) with the active site of PL, respectively. Thus, P32 could serve as promising lead compound for the development of more efficacious and selective pyrazolones-type PL inhibitors for biomedical applications.

PubMedSearch : Bao_2021_ChemMedChem__
PubMedID: 33527731

Related information

Citations formats

Bao X, Zhang J, Yang Y, Qian XK, Song PF, Zhao YS, Guan XQ, Zou LW, Wang H (2021)
Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors against Pancreatic Lipase
ChemMedChem :

Bao X, Zhang J, Yang Y, Qian XK, Song PF, Zhao YS, Guan XQ, Zou LW, Wang H (2021)
ChemMedChem :