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

• Published in: Bioorganic chemistry 2018-12, Vol.81, p.350-355
• Main Authors: Zhang, Juan, Liang, Jia-Hao, Zhao, Jian-Chao, Wang, Ya-Li, Dong, Pei-Pei, Liu, Xin-Guang, Zhang, Tian-Yuan, Wu, Ying-Ying, Shang, De-Jing, Zhang, Yi-Xuan, Sun, Cheng-Peng
• Format: Article
• Language: English
• Subjects: Benzophenones - chemistry; Benzophenones - isolation & purification; Carboxylesterase - antagonists & inhibitors; Carboxylesterase - chemistry; Catalytic Domain; Endophytic fungus; Humans; Inhibitory hCE 2 activity; Kinetics; Molecular docking; Molecular Docking Simulation; Secondary Metabolism; Secondary metabolites; Succinates - chemistry; Succinates - isolation & purification; Xylaria sp. SYPF 8246; Xylariales - chemistry; Xylariales - metabolism
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.07.019

•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. 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 IC50 values from 6.69 ± 0.85 µM to 29.78 ± 0.48 µM, respectively. [Display omitted] 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 Rh2(OCOCF3)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 IC50 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.