Qi Luo

(±)-Sinensilactam A, a Pair of Rare Hybrid Metabolites with Smad3 Phosphorylation Inhibition from Ganoderma sinensis

(+)- and (-)-Sinensilactam A (1), novel hybrid metabolites possessing a unique 2H-pyrrolo[2,1-b][1,3]oxazin-6(7H)-one ring system, were isolated from the fruit bodies of Ganoderma sinensis. The structures of these substances and absolute configurations at their stereocenters were assigned using spectroscopic and computational methods along with X-ray crystallographic analysis. A plausible pathway for the biosynthesis of 1 is proposed. (-)-1 was found to be a Smad3 phosphorylation inhibitor in TGF-β1 induced human renal proximal tubular cells.

Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear.

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.

Applanatumols A and B, meroterpenoids with unprecedented skeletons from Ganoderma applanatum

Applanatumols A (1) and B [(±)-2], two unique meroterpenoids with a novel spiro[benzofuran-2,2′-bicyclo[3.2.2]nonane] ring system and a naturally unusual dioxacyclopenta[cd]inden motif, respectively, were isolated from Ganoderma applanatum. Their structures were determined using spectroscopic data. In particular, the absolute configurations of 1 and 2 were assigned by X-ray diffraction analysis using the Flack parameter and ECD calculations, respectively. A plausible biosynthetic pathway for 1 and 2 is proposed. The biological activities of 1 and 2 against renal fibrosis were accessed in rat proximal tubular epithelial cells.

Identification of Compounds from the Water Soluble Extract of Cinnamomum cassia Barks and Their Inhibitory Effects against High-Glucose-Induced Mesangial Cells

The difficulty of diabetic nephropathy (DN) treatment makes prevention the best choice. Cinnamomum cassia barks, known as Chinese cinnamon or Chinese cassia, is one of the most popular natural spices and flavoring agents in many parts of the World. Since previous reports indicated that Chinese cinnamon extract could be used for the treatment of diabetes, we proposed that this spice may be beneficial for the prevention of DN. However, the responsible compounds need to be further identified. In this study, we isolated three new phenolic glycosides, cinnacassosides A–C (1-3), together with fifteen known compounds from the water soluble extract of Chinese cinnamon. The structures of the new compounds were identified by comprehensive spectroscopic evidence. Eleven compounds (6-9, 11, 13-18) were isolated from this spice for the first time, despite extensive research on this species in the past, which added new facets for the chemical profiling of this spice. These isolates were purposely evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells which are definitely implicated in DN. The results showed that compounds 4-8 could inhibit over secretion of IL-6, collagen IV and fibronectin against high-glucose-induced mesangial cells at 10 µM, suggesting that Chinese cinnamon could be used as a functional food against DN.

Spiro Meroterpenoids from Ganoderma applanatum

Spiroapplanatumines A-Q (1-12, 14-16, 18, and 20), new spiro meroterpenoids respectively bearing a 6/5/7 or 6/5/5 ring system, along with three known compounds, spirolingzhines A, B, and D, were isolated from the fruiting bodies of the fungus Ganoderma applanatum. Their structures including absolute configurations were assigned by using spectroscopic methods, ECD and 13C NMR calculations, and single-crystal X-ray diffraction analysis. Biological evaluation of all the compounds disclosed that compounds 7 and 8 inhibited JAK3 kinase with IC50 values of 7.0 ± 3.2 and 34.8 ± 21.1 μM, respectively.

Meroterpenoid enantiomers from Ganoderma sinensis.

Zizhines A-F (1-6), six pairs of new meroterpenoid enantiomers and a known meroterpenoid (7) were isolated from the fruiting bodies of Ganoderma sinensis. The structures and absolute configurations of the new substances were assigned by spectroscopic and computational methods. All the compounds apart from 7 were evaluated for their inhibition on extracellular matrix component (fibronectin) generation by using TGF-β1-induced rat kidney tubular epithelial cells. Although none of them was found to be active in these cells, the present findings add new facets for the chemistry of Ganoderma.

Ganotheaecolin A, a Neurotrophic Conjugated Ergosterol with a Naphtho[1,8-ef]azulene Scaffold from Ganoderma theaecolum

Ganotheaecolin A (1), a novel ergosterol with a rare naphtho[1,8-ef]azulene ring system, was isolated from the fruiting bodies of Ganoderma theaecolum. Its structure was determined by spectroscopic data and computational methods. Compound 1 represents a 6/6/7/5-fused carbon skeletal ergosterol typically formed by Wagner-Meerwein rearrangement, whose plausible biosynthetic pathway was briefly discussed. Finally, the neurotrophic activity of 1 was examined using PC12 cells.

Racemic alkaloids from the fungus Ganoderma cochlear

Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

New ursane-type triterpenoids from Clerodendranthus spicatus

Five new ursane-type triterpenoids, spicatusoids A-E (1, 3-6), and three known ones (2, 7, and 8), and a known oleanane-type triterpenoid (9) were isolated from the aerial parts of Clerodendranthus spicatus. Their structures were elucidated by spectroscopic methods. In particular, the structure of 3 including its absolute configuration was confirmed by single-crystal X-ray diffraction analysis. Cell viability of all the compounds against rat kidney fibroblast cells (NRK-49F) with or without TGF-β1 induction and human cancer cells (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) was examined by using MTT or MST assays. It was found that, with exception of 1, all the tested compounds could inhibit cell proliferation in TGF-β1 induced NRK-49F cells with compounds 2 being most active.

Two rare meroterpenoidal rotamers from Ganoderma applanatum

Applanatumols Z3 (1) and Z4 (2), two novel natural product hybrids consisting of a meroterpenoid and a glycerol and three known compounds (3–5) were isolated from the fruiting bodies of the fungus Ganoderma applanatum. Their structures were elucidated by means of spectroscopic methods, ECD and 13C NMR calculations. It is of particular interest that 1 and 2 are rare separable conformers. Racemic 1 and 2 were further separated by chiral HPLC to afford their respective enantiomers, whose biological activities were evaluated against JAK3 and DDR1 kinases.