a-Glucosidase inhibition and molecular docking studies of butyrolactone I derived from Aspergillus terreus and evaluation of its acute toxicity

Butyrolactone I (1), a major compound of Aspergillus terreus know has a wide range of biological activities. In this report, butyrolactone I (1) has been isolated along with aspernolide A (2), butyrolactone II (3), butyrolactone III (4) from liquid fermentation of A. terreus. Furthermore, a series of butyrolactone I (1) derivatives 1.1-1.3 have been synthesized, and all compounds obtained were evaluated for their in vitro a-glucosidase inhibitory activity. The interaction of those compounds to the active site of the a-glucosidase enzyme from Saccharomyces cerevisiae was studied by the docking method. Among all the compounds, compound 1 exhibited potential activities against a-glucosidase with IC50 of 53.92 µM, when compared with the standard quercetin having IC50 value 31.29 µM. Docking studies of 1 showed hydrogen bonding interactions with Ser-311, Glu-411, Glu-277, Gln-279, arene-anion, and arene-cation interactions. The promising potential as an a-glucosidase inhibitor compound 1, was then further tested for in vivo toxicities using the DDY mice. Observations were carried out for 14 days, with no mortality was recorded in both of the male group and the female group. The compound 1 is practically non-toxic for female DDY mice (LD50>2,000 mg/kg). Based on these results suggest that the compound 1, could be a promising lead compound in the search for development a new a-glucosidase agen for future drug development against diabetes mellitus.