Improving Retinoic Acid Efficacy: Lipase-Catalyzed Synthesis of Derivatives with Antiviral Activity.

Abstract

An efficient enzymatic approach was applied to the synthesis of new derivatives of retinoic acid. Nine derivatives, four of them new compounds, were obtained through lipase-catalysis with excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile : substrate ratio, enzyme : substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. In addition, several synthesized compounds exhibited lower cytotoxicity than the retinoic acid in Vero cells and a remarkably higher antiviral activity against Herpes simplex virus type 1 (HSV-1) and Herpes simplex virus type 2 (HSV-2).