Effect of 2,4-disubstituted thiazol-5yl-aminoketones on inflammation. In vitro and in vivo biological studies: a structure-activity approach.
Some modified novel thiazol-5yl-aminoketones were evaluated for their anti-inflammatory, analgesic and antiproteolytic activities. Their inhibitory activity on 12-lipoxygenase (12-LO) and beta-glucuronidase in vitro was estimated. Their interaction with the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and their RM values were also determined. For two of them, the effect on zoxazolamine-induced paralysis after a prolonged treatment was determined. The duration of paralysis for the same compounds, (only one administration, one before zoxazolamine injection) was recorded too. The 2-amino substituted derivatives seem to be more potent in comparison with the 2-phenyl. The tested compounds were found to influence proteolysis but not the activities at beta-glucuronidase and 12-LO. Their interaction with DPPH was mild. Compound 2 seems to modify the activity of the hepatic drug metabolizing enzymes. In conclusion, their activity is related to certain structural characteristics.
Hadjipavlou-Litina
D J
DJ
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.
Geronikaki
A A
AA
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D007928:Lethal Dose 50; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D015049:Zoxazolamine / Q000378:metabolism / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007659:Ketones; D016859:Lipoxygenase Inhibitors; D015049:Zoxazolamine; D005966:Glucuronidase