LIPO-PINOCEMBRIN DERIVATIVES AS NEW TOOLS IN WOUND HEALING DRUG DEVELOPMENT

Cutaneous wound healing, including diabetic foot ulcers, represents a very important medical problem, treated by using antibiotics and animal-derived compounds. The use of natural products, including fatty acids and polyphenols, is considered an innovative and low-cost tendency, especially for their interaction with the free fatty acid receptor 4 (GPCR120), abundant in the skin. Pinocembrin, representative of the flavanone family, is a suitable probe for GPR120, with browsable wound healing properties. In this field, five pinocembrin fatty acid acyl derivatives were synthesized as suitable GPR120 ligands through a lipase-catalyzed synthesis. The derivatives were able to increase wound healing dose-dependently, also in a reduced proliferation model. The most interesting resulted the linolenic ester, which is also able to stimulate TGF-beta production, a downstream signalling in GPR120 transduction. Further studies are ongoing to validate GPR120 as molecular target.