title: Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives.
abstract: N-Palmitoyl-ethanolamine (PEA) is an anti-inflammatory component of egg yolk that is usually employed for the prevention of respiratory apparatus virus infection and then frequently used for its efficient anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic, and inflammatory diseases. Nevertheless, data of its use in animal or human therapy are still scarce and further studies are needed. Herein, we report the biological evaluation of a small library ofN-palmitoyl-ethanolamine analogues or derivatives, characterized by a protected acid function (either as palmitoyl amides or hexadecyl esters), useful to decrease their hydrolysis rate in vitro and prolong their biological activity. Two of these compounds-namely phenyl-carbamic acid hexadecyl ester (4) and 2-methyl-pentadecanoic acid (4-nitro-phenyl)-amide (5)-have shown good anti-inflammatory and antioxidant properties, without affecting the viability of J774A.1 macrophages. Finally, crystals suitable for X-ray analysis of compound4have been obtained, and its solved crystal structure is here reported. Our outcomes may be helpful for a rational drug design based on new PEA analogues/derivatives with improved biological properties.
authors.affiliation: Department of Science, University of Basilicata, Viale dell'Ateneo Lucano 10, Potenza 85100, Italy. carmela.saturnino@unibas.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. apopolo@unisa.it.
authors.forename: Ada
authors.initials: A
authors.lastname: Popolo
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. aramunno@unisa.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Ramunno
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. sadesso@unisa.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Adesso
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. mipecoraro@unisa.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Pecoraro
authors.affiliation: Institute for the Study of Nanostructured Materials, ISMN-CNR, Palermo, c/o Department of ChiBioFarAm, University of Messina, Vill. S. Agata, Viale F. Stagno d'Alcontres 31, Messina 98166, Italy. rosaria.plutino@ismn.cnr.it.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Plutino
authors.affiliation: Department of Chemistry, University of Milano, Via Golgi 19, Milano 20133, Italy. silvia.rizzato@unimi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rizzato
authors.affiliation: Department of Chemistry, University of Milano, Via Golgi 19, Milano 20133, Italy. alberto.albinati@unimi.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Albinati
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. smarzocco@unisa.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy. msala@unisa.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende (CS) 87036, Italy. domenico.iacopetta@unical.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iacopetta
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende (CS) 87036, Italy. s.sinicropi@unical.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
mesh_terms: D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004983:Ethanolamines / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010169:Palmitic Acids / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol
keywords: N-acyl-ethanolamines; N-palmitoyl-ethanolamine derivatives; anti-inflammatory activity; antioxidant properties; biological evaluation of PEA derivatives; crystallographic studies