Abstract
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.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Arthritis, Experimental / drug therapy
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Carrageenan
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Coumarins / chemical synthesis*
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Coumarins / chemistry
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Coumarins / pharmacology
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry
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Edema / chemically induced
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Edema / drug therapy
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Female
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Free Radical Scavengers / chemical synthesis
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Free Radical Scavengers / chemistry
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Immunologic Factors / chemical synthesis
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Immunologic Factors / chemistry
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Immunologic Factors / pharmacology
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Lipoxygenase Inhibitors / chemical synthesis
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Lipoxygenase Inhibitors / chemistry
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Male
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Mannich Bases / chemical synthesis*
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Mannich Bases / chemistry
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Mannich Bases / pharmacology
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Rats
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Rats, Inbred F344
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Structure-Activity Relationship
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Superoxides / chemistry
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Coumarins
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Cyclooxygenase Inhibitors
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Free Radical Scavengers
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Immunologic Factors
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Lipoxygenase Inhibitors
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Mannich Bases
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Superoxides
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Carrageenan