Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2.

Highlights • Xylarianins A-D (1 – 4) were isolated from the fermentation broth of Xylaria sp. SYPF 8246. • The integrated 1H and 13C NMR data of three natural products 5 – 7 were reported for the first time. • All the isolated compounds were assayed for their inhibitory activities against hCE 2. • The inhibition kinetics of compounds 1 and 5 against hCE 2 have been studied in vitro. • Molecular docking revealed interaction of compounds 1 and 5 with hCE 2. Graphical abstract Four new metabolites, xylarianins A-D (1 – 4) were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246 together with three new natural products (5 – 7) and eleven known compounds (8 – 18). Compounds 1 , 5 – 9 , and 18 displayed significant inhibitory activities against hCE 2 with IC 50 values from 6.69 ± 0.85 µM to 29.78 ± 0.48 µM, respectively. Abstract Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1 – 4), three new natural products, 6-methoxycarbonyl-2 ′ -methyl-3,5,4′,6 ′ -tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2 ′ -rnethyl-3,5,4′,6 ′ -tetramethoxy-diphenyl ether (6), and 2-chlor-4 ′ -hydroxy-6-methoxy carbonyl-2 ′ -methyl-3,5,6 ′ -trimethoxy-diphenyl ether (7), and eleven known compounds (8 – 18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh 2 (OCOCF 3) 4 -induced electronic circular dichroism (ECD) spectra analyses. The integrated 1H and 13C NMR data of three new natural products 5 – 7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1 , 5 – 9 , and 18 displayed significant inhibitory activities against hCE 2 with IC 50 values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78, 29.78 ± 0.48, 18.86 ± 1.87, and 20.72 ± 1.51 µM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking. [ABSTRACT FROM AUTHOR]