title: Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.
abstract: Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Theodosis-Nobelos
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Malamati
authors.initials: M
authors.lastname: Kourti
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Gavalas
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: rekka@pharm.auth.gr.
authors.forename: Eleni A
authors.initials: EA
authors.lastname: Rekka
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006949:Hyperlipidemias / Q000188:drug therapy / Q000473:pathology; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000627:therapeutic use; D009025:Morpholines / Q000737:chemistry*; D051381:Rats; D014280:Triglycerides / Q000097:blood
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D009025:Morpholines; D014280:Triglycerides; C028971:thiamorpholine; D002784:Cholesterol
keywords: Hypolipidemic activity; Inflammation; Non steroidal anti-inflammatory drugs; Thiomorpholine amides; α-Lipoic acid