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

Abstract

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.

A New Epi-neoverrucosane-type Diterpenoid from the Liverwort Pleurozia subinflata in Borneo

“…The HMBC correlations of H 2 -C (11) to C (20); and H-C (14) to C (20) suggested the carboxylic carbon at C(10). These findings together with HMBC correlations of H 3 -C(18) to C(2), C(3), C(4) and C 5; and H 3 -C (19) to C(1), C(6), C(7) and C (8) permitted establishment for the planar structure of 1 (Fig. 2).…”

“…While, diterpenoids such as clerodanes, dolabellanes, fusicoccanes, kauranes, labdanes, pimaranes and others were found in numerous liverworts [6]. Recently several bioactive cyathane diterpenoids were discovered [7,8]. Cyathane is precursor structure for biosynthesis of the verrucosanetype diterpenoid, a fused 3,6,6,5-tetracyclic carbon skeleton [9].…”

A Holistic Approach to Determining Stereochemistry of Potential Pharmaceuticals by Circular Dichroism with β-Lactams as Test Cases

“…To ensure that the obtained results are comparable, we also simulated the electronic and vibrational CD spectra at different levels of approximation; however, for the discussion here, we selected only the ones that demonstrate the best fit with the experimental spectra, i.e., obtained at the ωB97X-D/6–311+G(d,p) level of theory with the PCM solvent model. Additional motivation for using this approximation level was prior identification of its effectiveness and accuracy in reproducing chiroptical spectral features of various organic molecules of synthetic and natural origin [ 26 , 39 , 40 , 41 , 42 , 43 , 44 ]. In our previous work on β-lactams, we also showed that using the PCM solvent model significantly impacted the assignments’ credibility [ 22 , 31 , 33 , 45 , 46 , 47 ].…”

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

“…The NO concentration was detected by the Griess reagent. 33 Quercetin was used as a positive control. BV-2 cells were seeded at the density of 1.5 × 10 5 cells per mL in 96-well culture plate and treated with each compound and LPS (1.0 μg mL −1 ) for 24 h. After that, 50 μL of cell-free supernatant was allowed to react with an equal volume of Griess reagent (Beyotime Institute of Biotechnology, Shanghai, China) for 15 min at room temperature in the dark.…”