Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates.

Abstract

Tranilast is an anti-inflammatory drug in use for asthma and atopic dermatitis. In studies over the last decade it has been revealed that tranilast can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. We report a structure-activity study aimed at optimizing the antifibrotic activity of tranilast. A series of cinnamoyl anthranilates were prepared and assessed for their ability to prevent TGF-beta-stimulated production of collagen in cultured renal mesangial cells. We reveal derivatives with improved potency and reduced cellular toxicity relative to tranilast. 3-Methoxy-4-propargyloxycinnamoyl anthranilate reduces albuminuria in a rat model of progressive diabetes, and thus has potential as an innovative treatment for diabetic nephropathy.

• Authors: Steven C Zammit, Alison J Cox, Renae M Gow, Yuan Zhang, Richard E Gilbert, Henry Krum, Darren J Kelly, Spencer J Williams
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 24 Pg. 7003-6 (Dec 15 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19879136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-methoxy-4-propargyloxycinnamoyl anthranilate
• Caffeic Acids
• Cinnamates
• ortho-Aminobenzoates
• Collagen
• tranilast

Topics

• Animals
• Caffeic Acids (chemistry, pharmacology, therapeutic use)
• Cinnamates (chemistry, pharmacology, therapeutic use)
• Collagen (antagonists & inhibitors)
• Diabetes Mellitus, Experimental (complications, drug therapy, pathology)
• Diabetic Nephropathies (drug therapy, pathology)
• Fibrosis
• Kidney (drug effects, pathology)
• Rats
• Rats, Sprague-Dawley
• ortho-Aminobenzoates (chemistry, pharmacology, therapeutic use)