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Neurodegenerative diseases are currently posing huge social, economic, and healthcare burdens among the aged populations worldwide with few and only palliative treatment alternatives available. Natural products continue to be a source of a vast array of potent neurotrophic molecules that could be considered as drug design starting points. The present study reports eight new isoindolinone and benzofuranone derivatives, for which we propose the trivial names, hericioic acids A-G ( 1 - 7 ) and hericiofuranoic acid ( 8 ), which were isolated from a solid culture (using rice as substrate) of the rare European edible mushroom Hericium flagellum . The chemical structures of these compounds were determined based on extensive 1D and 2D NMR spectroscopy along with HRESIMS analyses. The isolated compounds were assessed for their neurotrophic activity in rat pheochromocytoma cells (PC-12) to promote neurite outgrowth on 5 ng NGF supplementation; all the compounds increased neurite outgrowths, with compounds 3 , 4, and 8 exhibiting the strongest effects.

With heimionones A-E ( 1 - 5 ), five new terpenoids were isolated from submerged cultures of Heimiomyces sp. in addition to the previously described compounds hispidin, hypholomin B, and heimiomycins A and B. Planar structures of the metabolites were elucidated by 1D and 2D NMR in addition to HRESIMS data. While ROESY data assigned relative configurations, absolute configurations were determined by the synthesis of MTPA esters of 1 , 3 , and 5 . The [6.3.0] undecane core structure of compounds 3 - 5 is of the asteriscane-type, however, the scaffold of 1 and 2 with their bicyclo [5.3.0] decane core and germinal methyl substitution is, to our knowledge, unprecedented. Together with several new compounds that were previously isolated from solid cultures of this strain, Heimiomyces sp. showed an exceptionally high chemical diversity of its secondary metabolite profile.

New meroterpenoids bis-heimiomycins A-D ( 1 - 4 ) and heimiomycins D and E ( 5 and 6 ) were isolated from solid rice cultures of Heimiomyces sp., while new calamene-type sesquiterpenoids heimiocalamene A ( 7 ) and B ( 8 ) were isolated from shake cultures, respectively. Structures of the metabolites were elucidated by 1D and 2D NMR in addition to HRESIMS data. While relative configurations were assigned by ROESY data, absolute configurations were derived from the structurally related, previously described calamenes, which we herein name heimiocalamenes C-E ( 9 - 11 ). A plausible biosynthetic pathway was proposed for 1 - 6 , with a radical reaction connecting their central para -benzoquinone building block to calamene-sesquiterpenoids. Based on the assumption of a common biosynthesis, we reviewed the structure of the known nitrogen-containing derivative 11 , calling the validity of the originally proposed structure into question. Subsequently, the structure of 11 was revised by analysis of HMBC and ROESY NMR data. Only heimiomycin D ( 5 ) displayed cytotoxic effects against cell line KB3.1.

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf ) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported.

Five new drimane-type sesquiterpenoids were isolated from cultures of the tropical basidiomycetes, Perenniporia centrali-africana (originating from Kenya) and Cerrena sp. nov. (originating from Thailand). A new pereniporin A derivative ( 1 ), a new drimane-type sesquiterpene lactam ( 2 ), and the new 6,7-Dehydro-isodrimenediol ( 3 ) were isolated from P. centrali-africana. In parallel, the two new drimane-type sesquiterpene lactams 5 and 6 were isolated together with known isodrimenediol ( 4 ) from Cerrena sp. This is the first report of drimane-type sesquiterpene lactams from basidiomycetes. The structures were elucidated based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. The compounds were devoid of significant antimicrobial and cytotoxic activities.

A mycelial culture of the African basidiomycete Echinochaete cf. brachypora was studied for biologically active secondary metabolites, and four compounds were isolated from its crude extract derived from shake flask fermentations, using preparative high-performance liquid chromatography (HPLC). The pure metabolites were identified using extensive nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Aside from the new metabolites 1-methoxyneomarinone ( 1 ) and (E)-3-methyl-5-(-12,13,14-trimethylcyclohex-10-en-6-yl)pent-2-enoic acid ( 4 ), the known metabolites neomarinone ( 2 ) and fumaquinone ( 4 ) were obtained. Such compounds had previously only been reported from Actinobacteria but were never isolated from the cultures of a fungus. This observation prompted us to evaluate whether the above metabolites may actually have been produced by an endosymbiontic bacterium that is associated with the basidiomycete. We have indeed been able to characterize bacterial 16S rDNA in the fungal mycelia, and the production of the metabolites stopped when the fungus was sub-cultured on a medium containing antibacterial antibiotics. Therefore, we have found strong evidence that compounds 1 - 4 are not of fungal origin. However, the endofungal bacterium was shown to belong to the genus Ralstonia , which has never been reported to produce similar metabolites to 1 - 4 . Moreover, we failed to obtain the bacterial strain in pure culture to provide final proof for its identity. In any case, the current report is the first to document that polyporoid Basidiomycota are associated with endosymbionts and constitutes the first report on secondary metabolites from the genus Echinochaete .

Three previously undescribed compounds named heimiomycin A-C ( 1 - 3 ), featuring a unique scaffold with calamenene connected to a hydroxystyryl-pyranone moiety, along with the new calamenene derivatives 4 and 5 and phenanthridine derivative ( 6 ) were obtained from a culture of a Heimiomyces sp. This is the first report of the occurrence of calamenene-type terpenoids in fungi. Compound 3 exhibited antimicrobial activity against Gram-positive bacteria and Mucor hiemalis . Compounds 1 and 3 displayed moderate cytotoxicity against KB 3.1 and L929 cell lines, respectively.

During the course of searching for new anti-infective and other biologically active secondary metabolites from Kenyan basidiomycetes, 13 previously undescribed metabolites, (6 R,7 S,10 R)-7,10-epoxy-7,11-dimethyldodec-1-ene-6,11-diol (1) and 12 sesquiterpenes named elgonenes A-L (2-13), and the known compound P-coumaric acid (14) were isolated from a basidiomycete collected in Mount Elgon Natural Reserve. The producing organism represents a new species of the genus Sanghuangporus, which is one of the segregates of the important traditional Asian medicinal mushrooms that were formerly known as the " Inonotus linteus" complex. The structure elucidation of compounds 1-13, based on 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectral methods, and their antibacterial, antifungal, and cytotoxic activities are reported.

The need for effective compounds to combat antimicrobial resistance and biofilms which play important roles in human infections continues to pose a major health challenge. Seven previously undescribed acyclic diterpenes linked to isocitric acid by an ether linkage, microporenic acids A-G (1-7), were isolated from the cultures of a hitherto undescribed species of the genus Microporus (Polyporales, Basidiomycota) originating from Kenya's Kakamega forest. Microporenic acids D and E (4 and 5) showed antimicrobial activity against a panel of Gram positive bacteria and a yeast, Candida tenuis. Moreover, microporenic acids A and B (1 and 2) demonstrated dose-dependent inhibition of biofilm formation by Staphylococcus aureus. Compound 1 further showed significant activity against Candida albicans and Staphylococcus aureus preformed biofilms.

A mycelial culture of the Kenyan basidiomycete Fomitiporia aethiopica was fermented on rice and the cultures were extracted with methanol. Subsequent HPLC profiling and preparative chromatography of its crude extract led to the isolation of five previously undescribed pregnenolone type triterpenes 1 - 5 , for which we propose the trivial name aethiopinolones A-E. The chemical structures of the aethiopinolones were determined by extensive 1D- and 2D-NMR, and HRMS data analysis. The compounds exhibited moderate cytotoxic effects against various human cancer cell lines, but they were found devoid of significant nematicidal and antimicrobial activities., Competing Interests: The authors declare no conflict of interest.

Eight previously undescribed compounds were isolated and characterised from the supernatant and mycelium of a culture of the basidiomycete Favolaschia calocera originating from Kakamega equatorial rainforest in Kenya. These were: 9- oxostrobilurins A, G, K and I and the four monochlorinated calocerins A, B, C and D. The calocerins extend our knowledge of halogenated compounds obtained from natural sources. Four further known compounds were also identified: strobilurin G, favolon, pterulinic acid and 2,3 -dihydro-1-benzoxepin derivative. The four oxostrobilurins exhibited prominent antifungal and cytotoxic activities while the four calocerins only showed cytotoxic activity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)