Beauverolides and beauveriolides - from the use in traditional Chinese medicine to the sterol O-acyltransferase inhibition
Abstract
Nonribosomal peptide synthetases of various fungal species stay behind a broad spectrum of peptides, including penicillin and cyclosporine A. In the present contribution, we focus on cyclodepsipeptides, i.e., cyclic oligomeric molecules, in which one or more aminoacids are replaced with hydroxylated carboxyl acids.
We focus on cyclodepsipeptides termed beauverolides and beauveriolides that were isolated from entomopathogenic fungi. These compounds inhibit the sterol O-acyltransferase and display high affinity towards calmodulin.
The tests on cell lines and murine experimental models pointed towards the beauveriolide-induced inhibition of the sterol O-acyltransferase in the reduction of senile plaques that are characteristics for the Alzheimer disease and in the reduction of the conversion of macrophages to foam cells in the pathogenesis of atherosclerosis. The use of pure formulations of beauverolides and beauveriolides is complicated by their difficult solubility in aqueous solutions.
However, the already proven low toxicity of beauveriolides supports the translation of the research on beauveriolides into clinical studies. It is of interest that the mounting evidence on effects of beauverolides and beauveriolides correspond to effects for which their source organisms are used in traditional Chinese medicine.
