New alkaloids from the diversity-enhanced extracts of an endophytic fungus Aspergillus flavus GZWMJZ-288

Three new alkaloids (1-3) together with four previously reported compounds (4-7) were identified from the extracts and the diversity-enhanced extracts of the fermentation broth of the endophytic fungus, Aspergillus flavus GZWMJZ-288 associated with Garcinia muldflora. The structures of new compounds were respectively determined as 19-amino-19-dehydroxy 5-epi-alpha-cyclopiazonic acid (1), 2-hydroxymethyl-5-(3-oxobutan-2-yl)aminopyran-4(4H)-one (2) and 4-amino-2-hydroxymethylpyridin-5-ol (3) by spectroscopic analysis, ECD calculation and X-ray single crystal diffraction. Compounds 1 and 4 with 19-enamine were dynamic equilibrium of Z- and E-isomers in the solution but favored in Z- isomers in the solid state, while compound 7 with 19-enol was favored in Z- isomer in the solution but a mixture of Z- and E- isomers in solid state. This phenomenon could be explained by the quantum-mechanical energies calculations. Among the isolated compounds 1-7, compounds 1,4 and 7 with a rare 1,3,4,5-tetrahydro-1-azaacenaphtho [3,4-c] pyrrolizidine skeleton showed alpha-glucosidase inhibitory activity with the IC50 values of 41.97 +/- 0.97, 232.57 +/- 11.45 and 243.95 +/- 3.36 mu M, respectively, and the binding modes were performed by silico docking studies.

Automated summary

Three new alkaloids and four previously reported compounds were identified from the fermentation broth of the endophytic fungus associated with Garcinia muldflora. Some of these compounds showed inhibitory activity against alpha-glucosidase, with structural insights provided by spectroscopic analysis and quantum-mechanical energies calculations.