Adamantane derivatives of thiazolyl-N-substituted amide, as possible non-steroidal anti-inflammatory agents.
A series of adamantane derivatives of thiazolyl-N-substituted amides were synthesized in a three-step reaction and tested for anti-inflammatory activity as well as lipoxygenase and cycloxygenase inhibitory actions. Theoretical calculation of their lipophilicity, as ClogP was performed. The effect of the synthesized compounds on inflammation, using the carrageenin-induced mouse paw oedema model was studied and compared to indomethacin. In general, the studied compounds were found to be potent anti-inflammatory agents (29.6-81.5%). Anti-inflammatory activity was influenced by some structural characteristics of the synthesized compounds. The lipoxygenase inhibitory activity was tested by the conversion of sodium linoleate to 13-hydroperoxylinoleic acid. Low inhibitory activity was observed. Evaluation of COX-1 and COX-2 inhibitory activities of the compounds revealed a COX-1 inhibitory potential, comparable to that of naproxen for some of the compounds and a low to moderate COX-2 inhibitory potential. Comparison of the in vivo and in vitro results leads to the conclusion that most compounds of this series may be involved in other mechanisms of inflammation, too.
Kouatly
Omar
O
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessalonik 54124, Greece.
Geronikaki
Athina
A
Kamoutsis
Charalambos
C
Hadjipavlou-Litina
Dimitra
D
Eleftheriou
Phaedra
P
D000218:Adamantane / Q000031:analogs & derivatives*; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice
D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D000218:Adamantane