Neuraminidase Inhibitors from the Fermentation Broth of Phellinus linteus

Abstract

During a search for neuraminidase inhibitors derived from medicinal fungi, we found that the fermentation broth of Phellinus linteus exhibited potent neuraminidase inhibitory activity. Through bioassay-guided fractionation, two active compounds were purified from the ethyl acetate-soluble portion of the fermentation broth of P. linteus. These structures were identified as inotilone (1) and 4-(3,4-dihydroxyphenyl)-3-buten-2-one (2) by spectroscopic methods. Compounds 1 and 2 inhibited H1N1 neuraminidase activity with IC50 values of 29.1 and 125.6 µM, respectively, in a dose-dependent manner. They also exhibited an antiviral effect in a viral cytopathic effect reduction assay using MDCK cells. These results suggest that compounds 1 and 2 from the culture broth of P. linteus would be good candidates for the prevention and therapeutic strategies towards viral infections.

Chemical Constituents of the Culture Broth of Phellinus linteus and Their Antioxidant Activity

“…In the 13 C NMR spectrum, twelve carbons at δ 187.0, 180.9, 148.4, 145.7, 144.6, 125.0, 123.1, 118.2, 116.2, 112.3, 105.7, and 15.9 were evident. These spectral data were in good agreement with inotilone reported in the literature [ 20 , 21 ]. Consequently, compound 2 was identified as inotilone.…”

“…The 1 H NMR spectrum of compound 3 in CD 3 OD exhibited signals of five methines at δ 7.51 (d, J = 16.4 Hz), 7.07 (d, J = 2.4 Hz), 6.98 (dd, J = 2.4, 8.4 Hz), 6.78 (d, J = 8.4 Hz), and 6.54 (d, J = 16.4 Hz) and one singlet methyl at δ 2.32. These spectroscopic data matched well with 4-(3,4-dihydroxyphenyl)-3-buten-2-one, which was previously isolated from the culture broth of this strain and identified as a neuraminidase inhibitor [ 21 ].…”

“…Consequently, compound 2 was identified as inotilone. We previously isolated inotilone from the culture broth of this strain as a neuraminidase inhibitor [ 21 ].…”

A Review: The Bioactivities and Pharmacological Applications of Phellinus linteus

“…This role has been attributed to the biological activity of its various components, including polysaccharides, triterpenoids, polyphenols, and pyrans. Based on modern pharmacological studies, P. linteus is reported to have multifaceted biological activities, including anti-inflammatory [6,7,8,9,10,11,12,13,14], immunomodulatory [15,16,17,18,19], antioxidative [20,21,22,23,24,25,26], antimicrobial, and antiviral [27,28,29,30,31,32,33], as well as anticancer [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57], antidiabetic [58,59,60,61,62,63,64,65,66,67], hepatoprotective […”

Neuraminidase Inhibitors from the Fruiting Body of Phellinus igniarius

“…They produce various classes of bioactive secondary metabolites with unique chemical structures [ 5 6 ]. In previous studies, we reported the isolation of neuraminidase inhibitors from Phellinus baumii and P. linteus and their biological properties [ 7 8 9 ]. As part of an ongoing effort to identify neuraminidase inhibitors from medicinal fungi, we found that the methanolic extract of fruiting bodies of P. igniarius exhibited significant H3N2 neuraminidase inhibitory activity.…”