Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.
Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions.
Siskou
Ioanna C
IC
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
Rekka
Eleni A
EA
Kourounakis
Angeliki P
AP
Chrysselis
Michael C
MC
Tsiakitzis
Kariofyllis
K
Kourounakis
Panos N
PN
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology; D001713:Biphenyl Compounds; D001812:Blood-Brain Barrier / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005620:Freund's Adjuvant; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010851:Picrates / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000201:enzymology; D014280:Triglycerides / Q000097:blood
D000975:Antioxidants; D001713:Biphenyl Compounds; D002800:Cholinesterase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010851:Picrates; D014280:Triglycerides; D005620:Freund's Adjuvant; D002784:Cholesterol; C004931:1,1-diphenyl-2-picrylhydrazyl; D005978:Glutathione; D007052:Ibuprofen