Cyathane Diterpenes from Cultures of the Bird's Nest Fungus Cyathus hookeri and Their Neurotrophic and Anti-neuroinflammatory Activities.

Six new cyathane diterpenoids, cyahookerins A-F (1-6), as well as nine known analogues (7-15), were isolated from the liquid culture of the basidiomycete Cyathus hookeri. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD), and the absolute configurations of compounds 1 and 4 were determined by single-crystal X-ray crystallography. Compounds 1 and 2 represent the first unusual cyathane acetals featuring a dioxolane ring. Compounds 1-6 displayed differential nerve growth factor-induced neurite outgrowth-promoting activity in PC-12 cells at concentrations of 10 µM. In addition, cyahookerin B (2), cyathin E (9), cyathin B2 (12), and cyathin Q (13) showed significant nitric oxide production inhibition in Lipopolysaccharide (LPS)-activated BV-2 microglial cells with IC50 values of 12.0, 6.9, 10.9, and 9.1 µM, respectively. Similar binding modes of the four compounds were indicated by molecular-docking studies, and structure-activity relationships are discussed.

Characterization of isobutylhydroxyamides with NGF-potentiating activity from Zanthoxylum bungeanum.

Eight isobutylhydroxyamides, including three new (1-3), qinbunamides A-C, and five known sanshools (4-8), ZP-amide A (4), ZP-amide B (5), ZP-amide E (6), ZP-amide C (7), and ZP-amide D (8), were isolated from the pericarps of cultivated Zanthoxylum bungeanum Maxim, cultivated in Qinling mountain area, Shaanxi, China. The structures of all compounds were determined on the basis of spectroscopic techniques, including 1D and 2D NMR analysis and comparison with previously reported data. Compounds 1 and 2 are the first example of isobutylhydroxyamides containing an ethoxy group, and compound 3 is a rare C11 fatty acid-containing sanshool existing in genus Zanthoxylum. The tested compounds enhanced nerve growth factor (NGF)-mediated neurite outgrowth (neurotrophic activity) in rat pheochromocytoma (PC12) cells, but were inactive in the inhibitory effects on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and growth of HCT116 cells at concentrations of 50µM.

Antioxidant lignans from the roots of Vladimiria muliensis.

Three new lignans (1, 2, and 8) and ten known ones (3-7, 9-13) were isolated from the roots of Vladimiria muliensis. Their structures and configurations were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. The isolated compounds were evaluated for their antioxidant and antibacterial activities. The antioxidant activity was the greatest for lignans 7 and 10 with IC50 values of 11.2 and 7.3 µM against DPPH radical, and of 1.6 and 1.7 µM against ABTS+ radical, respectively. Moreover, 7 also displayed broad-spectrum antibacterial activity with MIC values around 7.25 µg/mL.

Hyperelatosides A-E, biphenyl ether glycosides from Hypericum elatoides, with neurotrophic activity.

Five new biphenyl ether glycosides, hyperelatosides A-E (1-5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7-15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1-15 were preliminarily evaluated in vitro.

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities.

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A-J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal Basidiomycete Cyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K-R (1-8), were isolated from the solid culture of C. africanus cultivated on cooked rice, together with three known congeners (9-11). The structures and the absolute configurations of the new compounds were elucidated through comprehensive NMR and HRESIMS spectroscopic data, electronic circular dichroism (ECD) data, and chemical conversion. Compounds 1 and 2 represent the first reported naturally occurring compounds with 4,9-seco-cyathane carbon skeleton incorporating an unprecedented medium-sized 9/7 fused ring system, while the 3,4-seco-cyathane derivative (3) was isolated from Cyathus species for the first time. All compounds were evaluated for their neurotrophic and anti-neuroinflammatory activity. All the isolates at 1-25 µM displayed differential nerve growth factor (NGF)-induced neurite outgrowth-promoting activity in PC-12 cells, while one of the compounds, allocyathin B2 (11), inhibited NO production in lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. In addition, molecular docking studies showed that compound 11 generated interactions with the inducible nitric oxide synthase (iNOS) protein.

Design, synthesis and biological evaluation of novel sesquiterpene mustards as potential anticancer agents.

Several novel series of sesquiterpene mustards (SMs) bearing nitrogen mustard and glutathione (GSH)-reactive α-methylene-γ-butyrolactone groups were successfully prepared for the first time and showed excellent antiproliferative activities in vitro. Among them, compounds 2e and 2g displayed the highest antiproliferative properties with IC50 values ranging from 2.5 to 8.7 µM. The selectivity of these two compounds was evaluated by SRB method against human cancer and normal hepatic cells (HepG2 and L02). The induction of apoptosis and effects on the cell cycle distribution with compounds 2e and 2g were investigated by Hoechst 33,258 staining and flow cytometry, which exhibited that they could induce selective cell apoptosis and cell cycle arrest in HepG2 and L02 cells. In addition, further investigation showed that compounds 2e and 2g could obviously inhibit the proliferation of HepG2 cells by inducing significant DNA cross-linking and depleting GSH in cell media. The good cytotoxicity and selectivity of compounds 2e and 2g pointed them as promising leads for anticancer drug design.