(+)-Usnic acid enamines with remarkable cicatrizing properties

Bioorg Med Chem. 2013 Apr 1;21(7):1834-43. doi: 10.1016/j.bmc.2013.01.045. Epub 2013 Feb 4.


Wound healing is a significant concern in many pathologies (post-surgeries, burns, scars) and the search for new chemical entities is advisable. The lichen compound (+)-usnic acid (1) has found application in dermatological and cosmetic preparations, due to its bacteriostatic and antioxidant activities. The compound has also been shown to stimulate the wound closure of keratinocyte monolayers at subtoxic doses. Here we describe the design and synthesis of usnic acid enamines (compounds 2-11), obtained through nucleophilic attack of amino acids or decarboxyamino acids at the acyl carbonyl of the enolized 1,3 diketone. The wound repair properties of these derivatives were evaluated using in vitro and in vivo assays. Compounds 8 and 9 combine low cytotoxicity with high wound healing performance, suggesting their possible use in wound healing-promoting or antiage skin preparations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / therapeutic use*
  • Anti-Infective Agents / toxicity
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use
  • Antioxidants / toxicity
  • Benzofurans / chemistry*
  • Benzofurans / therapeutic use*
  • Benzofurans / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Lichens / chemistry*
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing / drug effects*


  • Anti-Infective Agents
  • Antioxidants
  • Benzofurans
  • usnic acid