Α-Glucosidase INHIBITORY EFFECT OF SULOCHRIN FROM ASPERGILLUSTERREUS AND ITSBROMINATED DERIVATIVES

Abstract

Use of α-glucosidase inhibitorsis one of the therapeutic approaches for decreasing postprandial hyperglycemia. Sulochrin (1) from Aspergillus terreus as well as two synthetic sulochrin derivatives were assessed for antidiabetic activity against yeast and rat intestine α-glucosidase. Sulochrin showed potential inhibition against yeast α-glucosidase, through a non-competitive mode with an IC 50 value of 133.79 µM, and rat intestine α-glucosidase by uncompetitive mode with an IC 50 value of 144.59 µM.. Two synthetic derivatives of sulochrin were also prepared by bromination which resulted in dibromosulochrin (2) and tribromo-sulochrin (3). Preliminary SAR studies of sulochrin derivatives revealed that the yeast α-glucosidase inhibitory activity of compound 2 and 3 increased than 1 due to substitution of hydrogen atom with bromine with IC 50 values of 122.65 and 49.08 µM, respectively. However, the inhibitory activity against rat intestine α-glucosidase of 2 and 3 was decreased compared to 1. To the best our knowledge, this is the first report of structure-activity relationship of sulochrin and its derivatives as α-glucosidase inhibitors. These results suggested that sulochrin can potentially be used as a lead compound to develop new α-glucosidase inhibitor from microorganisms.

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

“…Reported α -glucosidase activities regarding several A. terrus -isolated metabolites within our literature review [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] have prompted us to further investigate the potentiality of identifying novel uncited hits with potential biological activity. Additionally, exploring the molecular aspects of the compound’s affinity/binding with human α -glucosidase biological targets through a sophisticated in silico study was rationalized in order to guide future lead optimization and development.…”

Isolation and Identification of α-Glucosidase Inhibitor From Aspergillus Terreus F38

“…Previous our study has shown that fungi of Aspergillus sp, can produce an α-glucosidase inhibitors. Butyrolactone I, II, and three synthetic butyrolactone I derivatives were isolated from A. Terre us MC751 cultured in Czapek-dox broth, showed potential activity toward α-glucosidase (Dewi, et al, 2014), sulochrin and its brominated derivated also produced by A. terreus RCC1 by solid state fermentation exhibition of significant activity against α-glucosidase (Dewi, et al, 2018) and rubrofusarin showed potential activity inhibited of mamalian α-glucosidase, which isolated from A. aculeatus cultured in potato dextrose broth (Dewi, et al, 2016). Continuing of our efforts to isolate potential a-glucosidase inhibitors from terestrial fungi, the objective of this study was to isolated active compound from A. terreus F38 which cultured in potato dextrose broth.…”