ArticlePloS one2012
Design and synthesis of potent N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitor as anti-inflammatory compounds.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Oral Adelmidrol Administration Up-Regulates Palmitoylethanolamide Production in Mice Colon and Duodenum through a PPAR-γ Independent Action.Metabolites · 2022Article
- N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα.Journal of neuroimmunology · 2021Article
- The retinoid X receptor α modulator K-80003 suppresses inflammatory and catabolic responses in a rat model of osteoarthritis.Scientific reports · 2021Article
- Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses.Frontiers in pharmacology · 2021Article
- LiposomalRSC advances · 2020Article
- Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems: an mRNA study.Scientific reports · 2020Article
- Natural Potent NAAA Inhibitor Atractylodin Counteracts LPS-Induced Microglial Activation.Frontiers in pharmacology · 2020Article
- Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives asMedChemComm · 2019Article
- A New Use for an Old Drug: Carmofur Attenuates Lipopolysaccharide (LPS)-Induced Acute Lung InjuryFrontiers in pharmacology · 2019Article
- Molecular mechanism of activation of the immunoregulatory amidase NAAA.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.BMC genomics · 2017Article
- Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase.Molecules (Basel, Switzerland) · 2016Article
- Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration.Frontiers in aging neuroscience · 2016Review
- N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution.Molecular neurobiology · 2015Review
- Activity-Based Probe for N-Acylethanolamine Acid Amidase.ACS chemical biology · 2015Article
- Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α.Scientific reports · 2015Article
- A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation.ACS chemical biology · 2015Article
- Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent.British journal of pharmacology · 2015Article
- Article
- The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides.Immunity · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme involved in biological deactivation of N-palmitoylethanolamide (PEA), which exerts anti-inflammatory and analgesic effects through the activation of nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-α). To develop selective and potent NAAA inhibitors, we designed and synthesized a series of derivatives of 1-pentadecanyl-carbonyl pyrrolidine (compound 1), a general amidase inhibitor. Structure activity relationship (SAR) studies have identified a compound 16, 1-(2-Biphenyl-4-yl)ethyl-carbonyl pyrrolidine, which has shown the highest inhibition on NAAA activity (IC(50) =2.12 ± 0.41 µM) and is characterized as a reversible and competitive NAAA inhibitor. Computational docking analysis and mutagenesis study revealed that compound 16 interacted with Asparagine 209 (Asn(209)) residue flanking the catalytic pocket of NAAA so as to block the substrate entrance. In vitro pharmacological studies demonstrated that compound 16 dose-dependently reduced mRNA expression levels of iNOS and IL-6, along with an increase of intracellular PEA levels, in mouse macrophages with lipopolysaccharides (LPS) induced inflammation. Our study discovered a novel NAAA inhibitor, compound 16, that could serve as a potential anti-inflammatory agent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.