Design, synthesis and evaluation of carbazole derivatives as PPARα/γ dual agonists and antioxidants

• Published in: Bioorganic & medicinal chemistry Vol. 13; no. 13; pp. 4279 - 4290
• Main Authors: Kumar, Rakesh, Ramachandran, Uma, Srinivasan, Krishnamoorthy, Ramarao, Poduri, Raichur, Suryaprakash, Chakrabarti, Ranjan
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2005; Elsevier Science
• Subjects: Animals; Antioxidant; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biological and medical sciences; Blood Glucose - drug effects; Carbazoles - chemical synthesis; Carbazoles - chemistry; Carbazoles - pharmacology; Cells, Cultured; Diabetes Mellitus, Type 2 - drug therapy; Drug Design; General and cellular metabolism. Vitamins; Humans; Hydroxycarbazoles; Hyperlipidemias - drug therapy; Hypoglycemic; Kidney - drug effects; Kidney - metabolism; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; Medical sciences; Mice; Mice, Obese; Pharmacology. Drug treatments; PPAR alpha - agonists; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR dual agonists; PPAR gamma - agonists; PPAR gamma - genetics; PPAR gamma - metabolism; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Transactivation; Transcriptional Activation; Triglycerides - blood; Lipid peroxidation; Hypoglycemic; Antioxidant; Hydroxycarbazoles; Transactivation; PPAR dual agonists; Agonist; Carbazole derivatives; Lipids; PPAR-γ receptor; Biological activity; PPAR-α receptor; Hypoglycemic agent; Animal; Chemical synthesis; Peroxisome proliferator activated receptor; Peroxidation
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.04.018

A series of hydroxycarbazole derivatives were synthesized and evaluated for PPARα/γ dual agonist as well as antioxidant activities. While most compounds showed good antioxidant activity, some compounds were identified as potential PPARα/γ dual agonists as well. Compounds 10a and 16 were found to be active in animal studies. A series of hydroxycarbazole derivatives were synthesized and evaluated for PPARα/γ dual agonist as well as antioxidant activities. While most compounds showed good antioxidant activity, some compounds were identified as potential PPARα/γ dual agonists as well. Compounds 10a and 16 were found to be active in animal studies.