Medicinal Chemistry

Inhibitory Activities of Guaianolides from the Seeds of Byrsonima Crassifolia against Protein Glycation In Vitro

Abstract

Rosa Martha Perez-Gutierrez, Alethia Muñiz-Ramirez, Irasema Anaya-Sosa, Teresa Cruz-Victoria and Jose Maria Mota-Flores

In-depth chromatographicinvestigation on the hexane extract of Byrsonima crassifolia led to the identification of eight new guaianolides. Structural elucidation was established on the basis of spectral data as; byrsonina C (1) to byrsonina J (8). In vitro inhibitory activity of the 1-8 on advanced glycationend products (AGEs), analysis of protein gels (SDS-PAGE) profile and by matrix assisted laser desorption ionization (MALDI) coupled to time of flight (TOF) analyzers mass spectra (MALDI lineal TOF MS) were evaluated. Guaianolides exhibited glycation inhibitory activity similar to that of aminoguanidine. The major mechanism implied in the inhibition of protein glycation by compounds 1-8 was attributed to their ability to react with carbonyls. SDS-PAGE profiles displayed inhibition of AGE generation, through inhibition of the crosslinked formation of AGEs, which was detectable for MALDI linear TOF MS as an intensity reduction of the dimerized band. We conclude that guaianolidesfrom Byrsonima crassifolia can efficiently inhibit AGEs formation and oxidative damage elicited by monosaccharides, suggesting that may prevent AGEs-mediated interaction with multiple targets involved in the pathogenesis of diabetes.