Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates
Steven C Zammit, Alison J Cox, Renae M Gow, Yuan Zhang, Richard E Gilbert, Henry Krum, Darren J Kelly, Spencer J Williams
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2009
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 ..View full abstract
We thank the National Health and Medical Research Council for financial support. Denis Scanlon is thanked for HPLC analysis.