Synthesis and antiinflammatory activity of coumarin derivatives.
The synthesis of several coumarin Mannich bases is described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity was determined experimentally by RPTLC method. All compounds were evaluated for their antiinflammatory and antioxidant activity and for their ability to inhibit in vitro lipoxygenase. The derivatives were found to present antioxidant and antiinflammatory activities. The tested derivatives inhibited carraggeenin-induced hind paw edema. They also significantly suppressed the arthritis induced by Freund's adjuvant. Compound 10, the most active in vivo, was found to possess protective properties against adjuvant-induced arthritis in rats. The biological in vitro activities were concentration dependent. Hydrophilicity, the presence of a free 7-OH, and steric requirements for the substituent at position 8 are the most important factors in terms of SAR. An attempt was made to correlate several physicochemical properties of the molecules with their in vivo/in vitro activity.
Kontogiorgis
Christos A
CA
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
Hadjipavlou-Litina
Dimitra J
DJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003374:Coumarins; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D007155:Immunologic Factors; D016859:Lipoxygenase Inhibitors; D008352:Mannich Bases; D013481:Superoxides; D002351:Carrageenan