ABSTRACT
We present an efficient approach to the synthesis of a series of glycyrrhetinic acid derivatives. Six derivatives, five of them new compounds, were obtained through chemoenzymatic reactions in very good to 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. Moreover, in order to explain the reactivity of glycyrrhetinic acid and the acetylated derivative to different nucleophiles in the enzymatic reactions, molecular docking studies were carried out. In addition, one of the synthesized compounds exhibited remarkable antiviral activity against TKâ¯+â¯and TK- strains of Herpes simplex virus type 1 (HSV-1), sensitive and resistant to acyclovir (ACV) treatment.
Subject(s)
Antiviral Agents/pharmacology , Glycyrrhetinic Acid/pharmacology , Herpesvirus 1, Human/drug effects , Lipase/metabolism , Molecular Docking Simulation , Acyclovir/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Biocatalysis , Candida/enzymology , Carica/enzymology , Dose-Response Relationship, Drug , Eurotiales/enzymology , Glycyrrhetinic Acid/chemistry , Glycyrrhetinic Acid/metabolism , Microbial Sensitivity Tests , Molecular Structure , Rhizomucor/enzymology , Rhizopus/enzymology , Structure-Activity RelationshipABSTRACT
A series of cholic acid derivatives was synthesized by enzyme catalysis. Eleven acetyl and ester derivatives of cholic acid, eight of them new compounds, were obtained through regioselective lipase-catalyzed reactions in very good to excellent yield. The influence of various reaction parameters in the enzymatic esterification, acetylation and alcoholysis reactions, such as enzyme source, alcohol or acylating agent: substrate ratio, enzyme: substrate ratio, solvent and temperature, was studied. Moreover, in order to shed light to cholic acid behavior in the enzymatic reactions, molecular docking of the lipase with cholic acid and some derivatives was carried out.