Alternarin A (1), a rearranged drimane meroterpenoid characterized by a thioglycerate moiety, was isolated together with two known analogues from the coralassociated fungi Alternaria sp. ZH-15. Its structure was determined based on spectroscopic analysis, modified Mosher's method, and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, compound 1 effectively inhibited the activity of spontaneous synchronous Ca 2+ oscillations and 4-aminopyridine induced epileptic discharges in the low micromolar concentration range.
AbstractEpilepsy is a serious chronic neurologic disorder characterized by recurrent unprovoked seizures resulting from abnormal and highly synchronous neuronal discharges within the brain. Small noncoding RNAs, called microRNAs, play vital roles in epileptogenesis, with potential contributions as valuable biomarkers and targets for the treatment of epilepsy. To maintain cellular homeostasis, cellular components, such as organelles, proteins, protein complexes/oligomers, and pathogens, are delivered to the lysosome for degradation through a process called autophagy, which plays either a protective or a harmful role under epileptic stress. Several autophagic mechanisms have been implicated in epileptogenesis, including the mammalian target of rapamycin pathway, aberrant substrate accumulation, and the formation of epileptic networks. In addition, the regulation of autophagy through microRNAs (miRNAs) represents a novel posttranscriptional regulatory mechanism through ‘autophagamiRNAs’. The correlation between autophagy and miRNA has increased our understanding of the underlying pathogenesis of human diseases. Here, we review the current findings regarding the correlations between miRNA, autophagy, and epilepsy to provide a solid foundation for further examination of the miRNA-autophagy pathway involved in epilepsy pathophysiology.
Swinhoeisterols C-F (1-4), four new steroids having a rearranged 6/6/5/7 ring system, were isolated from the Xisha sponge Theonella swinhoei, together with the known analogue swinhoeisterol A (5). Their structures were determined based on spectroscopic analysis, TDDFT-ECD and optical rotation calculations, and biogenetic correlations. In an in vitro assay, compound 1 showed an inhibitory effect on (h)p300 with an IC value of 8.8 μM, whereas compounds 2-4 were not active.
Two new anthraquinone derivatives, alterporriol Y (1) and macrosporin 2-O-α-D-glucopyranoside (2), together with five known analogues (3-7) were isolated from the fungus Stemphylium lycopersici associated with the gorgonian coral Dichotella gemmacea collected from the South China Sea. Their structures were determined on the basis of detailed spectroscopic analysis and comparison with reported data. The absolute configurations were determined by the ECD method. In an in vitro cytotoxic assay, compound 3 and 4 showed potent effects against HCT-116 and MCF-7 cell lines. Compound 4 also exhibited cytotoxicity toward Huh7 stem cell-like cells.
Seven new briarane diterpenoids, gemmacolides AS-AY (1–7), were isolated together with ten known analogues (8–17) from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data and comparison with reported data. The absolute configuration of compounds was determined based on electronic circular dichroism (ECD) experiments and genetic correlations as well. Compounds 15 and 16 were reported for the first time for the gorgonian. In the preliminary in vitro bioassays, compound 5 showed potential growth inhibitory activity against MG63 cells.
Four new briarane diterpenoids, junceellolides M–P (1–4), were isolated together with seven known analogs (5–11) from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1–3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.
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