Ursolic Acid Derivatives as Potential Agents Against Acanthamoeba Spp.
Fecha
2019Resumen
The current chemotherapy of Acanthamoeba keratitis relies on few drugs with low potential
and limited e cacy, for all this there is an urgent need to identify new classes of anti-Acanthamoeba
agents. In this regard, natural products play an important role in overcoming the current need and
medicinal chemistry of natural products represents an attractive approach for the discovery and
development of new agents. Ursolic acid, a natural pentacyclic triterpenoid compound, possesses a
broad spectrum of activities including anti-Acanthamoeba. Herein, we report on the development by
chemical transformation of an ursolic acid-based series of seven compounds (2–8), one of them reported
for the first time. The structure-activity relationship (SAR) analysis of their anti-Acanthamoeba activity
revealed that acylation/ether formation or oxidation enhances their biological profile, suggesting
that the hydrophobic moiety contributes to activity, presumably by increasing the a nity and/or cell
membrane permeability. These ursolic acid derivatives highlight the potential of this source as a good
base for the development of novel therapeutic agents against Acanthamoeba infections.