(+)-Usnic acid enamines with remarkable cicatrizing properties


Bruno M., Trucchi B., Burlando B., Ranzato E., Martinotti S., AKKOL E. , ...More

BIOORGANIC & MEDICINAL CHEMISTRY, vol.21, no.7, pp.1834-1843, 2013 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 7
  • Publication Date: 2013
  • Doi Number: 10.1016/j.bmc.2013.01.045
  • Title of Journal : BIOORGANIC & MEDICINAL CHEMISTRY
  • Page Numbers: pp.1834-1843
  • Keywords: (+)-Usnic acid, Mannich bases, Scratch wound assay, In vivo wound healing assays, Wound healing therapy, HUMAN DERMAL FIBROBLASTS, USNIC ACID, HACAT KERATINOCYTES, ELASTASE ACTIVITY, NATURAL-PRODUCTS, LICHEN, RATS, EXTRACT, AGENTS, MICE

Abstract

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. (C) 2013 Elsevier Ltd. All rights reserved.