Phellintremulins A-C, antinociceptive sesquiterpenoids from the medicinal fungus Phellinus tremulae

• Published in: Phytochemistry (Oxford) Vol. 223; p. 114112
• Main Authors: Tian, Chun, Sun, Li-Tang, Jin, Tian, Yuan, Lin-Lin, Xu, Wei-Fang, Yang, Hui-Xiang, Feng, Tao, Liu, Ji-Kai
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2024; Elsevier
• Subjects: Analgesic activity; Analgesics - chemistry; Analgesics - isolation & purification; Analgesics - pharmacology; Animals; Basidiomycota - chemistry; Biochemistry & Molecular Biology; Dose-Response Relationship, Drug; Life Sciences & Biomedicine; Male; Mice; Molecular Structure; Phellintremulin; Phellinus tremulae; Plant Sciences; Polyporales; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenoids; Structure-Activity Relationship; Phellinus tremulae; Phellintremulin; Polyporales; Sesquiterpenoids; Analgesic activity; PRODUCTS; CULTURES
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2024.114112

Phellintremulin A (1), a rearranged sesquiterpenoid with an unprecedented bicyclic backbone, and two previously unreported illudane-type sesquiterpenoids, namely phellintremulin B (2) and phellintremulin C (3), together with two known analogues (±)‒4 and (±)‒5, were isolated from cultures of the medicinal fungus Phellinus tremulae. Their structures and absolute configurations were established by means of spectroscopic data and HRESIMS analyses, as well as ECD and NMR calculations. A plausible biogenesis for 1 was discussed. The electrophysiological experiments showed that phellintremulins (A‒C) can inhibit Nav current in DRG neuron cells at 10 μM, with percentage inhibitions of 23.2%, 49.3%, and 31.7%, respectively. The antinociceptive activities of phellintremulins (A‒C) were evaluated via the acetic acid-induced writhing test in mice at a dose of 3 mg/kg. They showed significant antinociceptive effects with percentages of inhibition of 43.8%, 54.4%, and 50.6%, respectively, and phellintremulin B and C expressed more potent analgesic effect than lidocaine. Three undescribed sesquiterpenoids and two analogues were isolated from the medicinal fungus Phellinus tremulae. Phellintremulins A possessed a rare rearranged bicyclic carbon skeleton. Phellintremulins A‒C exhibited significant analgesic effects in an acetic acid-induced writhing test. [Display omitted] •Three undescribed compounds were isolated from the fungus Phellinus tremulae.•Their structures were confirmed by NMR spectra, ECD and 13C NMR calculation.•Phellintremulin A possessed a rare 6/6 bicyclic sesquiterpenoid skeleton.•Phellintremulins A‒C exhibited significant analgesic effects.