Identification of 2,4-Dinitro-Biphenyl-Based Compounds as MAPEG Inhibitors.
ChemMedChem
; 17(22): e202200327, 2022 11 18.
Article
in En
| MEDLINE
| ID: mdl-36111583
ABSTRACT
We identified 2,4-dinitro-biphenyl-based compounds as new inhibitors of leukotriene C4 synthase (LTC4 S) and 5-lipoxygenase-activating protein (FLAP), both members of the "Membrane Associated Proteins in Eicosanoid and Glutathione metabolism" (MAPEG) family involved in the biosynthesis of pro-inflammatory eicosanoids. By molecular docking we evaluated the putative binding against the targets of interest, and by applying cell-free and cell-based assays we assessed the inhibition of LTC4 S and FLAP by the small molecules at low micromolar concentrations. The present results integrate the previously observed inhibitory profile of the tested compounds against another MAPEG member, i. e., microsomal prostaglandin E2 synthase (mPGES)-1, suggesting that the 2,4-dinitro-biphenyl scaffold is a suitable molecular platform for a multitargeting approach to modulate pro-inflammatory mediators in inflammation and cancer treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biphenyl Compounds
/
Glutathione Transferase
Type of study:
Diagnostic_studies
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2022
Document type:
Article
Affiliation country: