Design and Synthesis of Novel Quinolinone-3-aminoamides and Their α-Lipoic Acid Adducts as Antioxidant and Anti-inflammatory Agents

• Published in: Journal of medicinal chemistry Vol. 50; no. 10; pp. 2450 - 2458
• Main Authors: Detsi, Anastasia, Bouloumbasi, Dionysia, Prousis, Kyriakos C, Koufaki, Maria, Athanasellis, Giorgos, Melagraki, Georgia, Afantitis, Antreas, Igglessi-Markopoulou, Olga, Kontogiorgis, Christos, Hadjipavlou-Litina, Dimitra J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 17-05-2007
• Subjects: Amides - chemical synthesis; Amides - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Biological and medical sciences; Biphenyl Compounds - chemistry; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan; Dimethyl Sulfoxide - chemistry; Edema - chemically induced; Edema - drug therapy; Female; Hydrazines - chemistry; Hydroxyl Radical - chemistry; Lipoxygenase Inhibitors - chemical synthesis; Lipoxygenase Inhibitors - pharmacology; Male; Medical sciences; Oxidation-Reduction; Pharmacology. Drug treatments; Picrates; Quinolones - chemical synthesis; Quinolones - pharmacology; Rats; Rats, Inbred F344; Structure-Activity Relationship; Thioctic Acid - analogs & derivatives; Thioctic Acid - chemical synthesis; Thioctic Acid - pharmacology; Edema; Thioctic acid; Rat; Enzyme; Aminoamide; Rodentia; Antiinflammatory agent; Lactam; Quinoline derivatives; Antioxidant; In vitro; In vivo; Vertebrata; Mammalia; Structure activity relation; Animal; Inhibitor; Oxidoreductases; Lipoxygenase; Chemical synthesis; Molecular adduct; Lipophilicity; Physicochemical properties; Quinolone derivatives
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm061173n

A series of N-substituted-quinolinone-3-aminoamides and their hybrids containing the α-lipoic acid functionality were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity. The new compounds were evaluated for their antioxidant activity and for their ability to inhibit in vitro lipoxygenase as well as for their anti-inflammatory activity in vivo. In general, the derivatives were found to be potent antioxidant or anti-inflammatory agents. The results are discussed in terms of structure−activity relationships and an attempt is made to define the structural features required for activity.