1. Development of new inhibitors for N-acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer
- Author
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Roberta Ottria, Riccardo Vago, Arianna Bettiga, Andrea Salonia, Pierangela Ciuffreda, Vago, Riccardo, Bettiga, Arianna, Salonia, Andrea, Ciuffreda, Pierangela, and Ottria, Roberta
- Subjects
0301 basic medicine ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Antineoplastic Agent ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,N-Acylethanolamine ,Drug Discovery ,Ethanolamine ,Amidohydrolase ,chemistry.chemical_classification ,Cell Death ,Molecular Structure ,N-acylethanolamine-hydrolyzing acid amidase ,Bladder cancer ,Recombinant Protein ,Endocannabinoid system ,Recombinant Proteins ,Cell biology ,Enzyme inhibition ,Ethanolamines ,030220 oncology & carcinogenesis ,Urinary Bladder Neoplasm ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Human ,Programmed cell death ,Antineoplastic Agents ,Amidohydrolases ,Amidase ,Structure-Activity Relationship ,03 medical and health sciences ,medicine ,Humans ,Molecular Biology ,Endocannabinoid ,Cell Proliferation ,Dose-Response Relationship, Drug ,Cell growth ,Drug Discovery3003 Pharmaceutical Science ,Organic Chemistry ,Cancer ,medicine.disease ,030104 developmental biology ,Enzyme ,Urinary Bladder Neoplasms ,chemistry ,Drug Screening Assays, Antitumor - Abstract
The endocannabinoid system is a signaling system involved in a wide range of biological effects. Literature strongly suggests the endocannabinoid system role in the pathogenesis of cancer and that its pharmacological activation produces therapeutic benefits. Last research promotes the endocannabinoid system modulation by inhibition of endocannabinoids hydrolytic enzymes instead of direct activation of endocannabinoid receptors to avoid detrimental effects on cognition and motor control. Here we report the identification of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines. These molecules were designed, synthesized and characterized and active compounds were selected by a fluorescence high-throughput screening method set-up on human recombinant NAAA that also allows to characterize the mechanism of inhibition. Together our results suggest an important role for NAAA in cell migration and in inducing tumor cell death promoting this enzyme as pharmacological target against bladder cancer.
- Published
- 2017