Synthesis and anti-inflammatory activity of chalcones and related Mannich bases.
Chalcones and Mannich bases have been reported to present antiinflammatory activities as well as inhibitory activities on several factors implicated in inflammation disorders. A series of chalcones and some related Mannich bases were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde. Mannich bases were derived from chalcones, with formaldehyde and the corresponding amine. The compounds were tested in vitro for their ability to inhibit various enzymes involved in the arachidonic acid cascade, for their antioxidant behaviour and in vivo for anti-inflammatory activity. Some chalcones and Mannich bases present strong anti-inflammatory and antioxidant activities. Almost all the tested compounds present high inhibitory activity on lipid peroxidation. Some compounds showed potent inhibitory effect on superoxide anion formation. Among the tested compounds 5 and 6 showed the highest lipoxygenase (LO) inhibitory activity. All the tested compounds inhibit both the proteolytic and esteratic activities of trypsin and chymotrypsin. The results indicated that the anti-inflammatory effects of the compounds were partially mediated, through their antioxidant activity. Attempts to correlate quantitatively structure with activity revealed that lipophilicity and molar refractivity influence the biological response.
Maria
Kouskoura
K
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
Dimitra
Hadjipavlou-Litina
HL
Maria
Giakoumakou
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002351:Carrageenan; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology*; D002918:Chymotrypsin / Q000737:chemistry; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004950:Esterases / Q000037:antagonists & inhibitors; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D007202:Indicators and Reagents; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology*; D010851:Picrates / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013481:Superoxides / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D047188:Chalcones; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D008055:Lipids; D008352:Mannich Bases; D010851:Picrates; D017382:Reactive Oxygen Species; D013481:Superoxides; D006418:Heme; D002351:Carrageenan; C004931:1,1-diphenyl-2-picrylhydrazyl; D004950:Esterases; D002918:Chymotrypsin; D005978:Glutathione