2. Academic Validation
  3. Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates

Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates

  • Bioorg Med Chem Lett. 2009 Dec 15;19(24):7003-6. doi: 10.1016/j.bmcl.2009.09.120.
Steven C Zammit 1,  Alison J Cox,  Renae M Gow,  Yuan Zhang,  Richard E Gilbert,  Henry Krum,  Darren J Kelly,  Spencer J Williams
Affiliations

Affiliation

  • 1 School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
PMID: 19879136 DOI: 10.1016/j.bmcl.2009.09.120
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.

Figures
Products