α-Glucosidase inhibitors from Malbranchea flavorosea

Diabetes mellitus is a metabolic disorder characterized by chronic high blood glucose levels, and is estimated as one of the most challenging health problems of the 21st century. The drugs available to lower hyperglycemia, focus on increasing insulin levels, improving sensitivity to the hormone in tissues, or reducing the rate of carbohydrate absorption from the gastrointestinal tract. The last group of drugs includes the inhibitors of α-glucosidases. In recent years, the search for new α-glucosidase inhibitors (αGI) structurally unique and biologically active from natural sources has increased notably [1]. As a part of our continuing effort to discover new α-glucosidases from natural sources [2, 3], we have now investigated Malbranchea flavorosea (ATCC 34529). Biodirected fractionation of the organic extract of M. flavorosea grown in rice medium, led to the isolation of three active compounds, identified as xylarinol A (1) [4], xylarinol B (2) [5] and massarigeninen C (3) [6]. Their spectroscopic and spectrometric data was compared to that previously reported on literature.

The α-glucosidase inhibitory activity was demonstrated with yeast and rat small intestinal α-glucosidases using a well-known spectrophotocolorimetric assay [6]. The three compounds showed inhibitory activity on mammalian α-glucosidases with half maximal inhibitory concentrations (IC₅₀) ranging from 1.05 to 1.19 mM, less active than acarbose (IC₅₀ 0.362 mM) used as positive control, but comparable to most natural products reported as αGI. This is the first report of αGI activity for these natural products, and represents the first chemical study of M. flavorosea, contributing to the chemical knowledge of the genus Malbranchea.

Acknowledgements: This work was supported by a grant from CONACyT (219765).

Keywords: Malbranchea flavorosea, α-glucosidase inhibitors, xylarinol.

References:

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No conflict of interest has been declared by the author(s).