title: A new therapeutic approach in Alzheimer disease: some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics.
abstract: The increasing life expectancy in our population makes Alzheimer's disease (AD) a growing public health problem. There is a great need to find a way to prevent and delay the disease. It was shown that monoamine oxidase-B (MAO-B) inhibitors and antiinflammatory agents might be effective in treating AD. Therefore, a novel series of 1-thiocarbamoyl-3-substituted phenyl-5-(2-pyrrolyl)-4,5-dihydro-(1H)-pyrazole derivatives as promising MAO-B inhibitors was synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). Most of the synthesized compounds showed high activity against both the MAO-A (compounds 3e-3h) and the MAO-B (compounds 3i-3l) isoforms. All the synthesized compounds were also tested for their in vivo antiinflammatory activity by two different bioassays namely, carrageenan-induced oedema and acetic acid-induced increase in capillary permeability in mice. In addition, analgesic and ulcerogenic activities were determined. The combined antiinflammatory data from in vivo animal models showed that compound 3k exhibited anti-inflammatory activity comparable to that of indomethacin with no ulcerogenic effects. Since compound 3k exhibits both antiinflammatory-analgesic activity and MAO-B inhibition, it needs further detailed studies.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Sihhiye, Ankara, Turkey. onesrin@hacettepe.edu.tr
authors.forename: Nesrin
authors.initials: N
authors.lastname: Gökhan-Kelekçi
authors.forename: Samiye
authors.initials: S
authors.lastname: Yabanoğlu
authors.forename: Esra
authors.initials: E
authors.lastname: Küpeli
authors.forename: Umut
authors.initials: U
authors.lastname: Salgin
authors.forename: Ozen
authors.initials: O
authors.lastname: Ozgen
authors.forename: Gülberk
authors.initials: G
authors.lastname: Uçar
authors.forename: Erdem
authors.initials: E
authors.lastname: Yeşilada
authors.forename: Engin
authors.initials: E
authors.lastname: Kendi
authors.forename: Akgül
authors.initials: A
authors.lastname: Yeşilada
authors.forename: A Altan
authors.initials: AA
authors.lastname: Bilgin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D006614:Hindlimb / Q000187:drug effects; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D008995:Monoamine Oxidase