Inhibition of the carbohydrate-hydrolyzing enzymes alpha-amylase and alpha-glucosidase by hydroxylated xanthones

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Santos, CMM (Autor) Outra; Proenca, C (Autor) Outra; Freitas, M (Autor) Outra; Araujo, AN (Autor) FFUP; Silva, AMS (Autor) Outra; Eduarda Fernandes (Autor) FFUP

Revista

Título: Food and Function

Vol. 13

Páginas: 7930-7941

ISSN: 2042-6496

Editora: Royal Society of Chemistry

Indexação

ISI Web of Knowledge - 0 Citações

Scopus

Outras Informações

ID Authenticus: P-00W-TSK

DOI: 10.1039/d2fo00023g

Abstract (EN): Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as alpha-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes alpha-amylase and alpha-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), alpha-mangostin (5) and gamma-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against alpha-glucosidase rather than for alpha-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of alpha-amylase, while xanthones 2c, 3b and 3c were the most active against alpha-glucosidase activity, with IC50 values lower than 10 mu M. These findings suggest that the substitution pattern of the xanthone scaffold modulated the inhibitory activity of these compounds, and some structure-activity relationships could be established for both assays. In addition, the type of inhibition was also studied, and the results indicate a competitive type of inhibition for alpha-amylase activity by xanthones 2c, 3b, 3c and gamma-mangostin (6). On the other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1-6 against alpha-glucosidase. The present work can open a promising area of research based on the design of novel xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism and therefore in the management of type 2 diabetes mellitus.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12