Novel drimane-type sesquiterpenoids and nucleosides from the Helicoma septoconstrictum suppress the growth of ovarian cancer cells.

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals.

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria.

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.

Morphophylogenetic evidence reveals four new fungal species within Tetraplosphaeriaceae (Pleosporales, Ascomycota) from tropical and subtropical forest in China.

Tetraplosphaeriaceae (Pleosporales, Ascomycota) is a family with many saprobes recorded from various hosts, especially bamboo and grasses. During a taxonomic investigation of microfungi in tropical and subtropical forest regions of Guizhou, Hainan and Yunnan provinces, China, several plant samples were collected and examined for fungi. Four newly discovered species are described based on morphology and evolutionary relationships with their allies inferred from phylogenetic analyses derived from a combined dataset of LSU, ITS, SSU, and tub2 DNA sequence data. Detailed illustrations, descriptions and taxonomic notes are provided for each species. The four new species of Tetraplosphaeriaceae reported herein are Polyplosphaeriaguizhouensis, Polyplosphaeriahainanensis, Pseudotetraploayunnanensis, and Tetraploahainanensis. A checklist of Tetraplosphaeriaceae species with available details on their ecology is also provided.

New Spirostane from a Fungus Neohelicomyces hyalosporus and Its Bioactivity.

A new spirostane, namely neohelicomyine B (1), together with six known steroids (2-7) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1-7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC50 value of 8.4±2.1 µM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC50 value of 3.0±0.2 µM.

New Guaiane-Type Sesquiterpenoids Biscogniauxiaols A-G with Anti-Fungal and Anti-Inflammatory Activities from the Endophytic Fungus Biscogniauxia Petrensis.

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A-G (1-7) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1-7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1, 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 µM, and suppressed nitric oxide (NO) production with IC50 ranging from 4.60 to 20.00 µM. Additionally, all compounds (100 µg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1, 2, and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal (C. albicans) and anti-inflammatory purposes.

Neogrisphenol A, a Potential Ovarian Cancer Inhibitor from a New Record Fungus Neohelicosporium griseum.

From the rice fermentation product of a new record fungus, Neohelicosporium griseum, two new polyketides, neogrisphenol A (1) and neogrisphenol B (2), one new isochroman-1-one, (S)-6-hydroxy-7-methoxy-3,5-dimethylisochroman-1-one (3), and four known compounds (4-7) were isolated. Their structures were determined using 1D- and 2D-NMR, mass spectrometry, and chemical calculations. The C-3~C-2' polymerization mode between the two α-naphthalenone derivative moieties is uncommon in compounds 1 and 2. Meanwhile, compounds 1-2 and 5 exhibited antibacterial activity against Bacillus subtilis, Clostridium perfringens, Staphylococcus aureus, and Staphylococcus aureus, with MIC values ranging between 16 and 31 µg/mL. In addition, compound 5 showed antifungal activity against Sclerotinia sclerotiorum and Phytophthora nicotianae var. nicotianae, with respective IC50 values of 88.14 ± 2.21 µg/mL and 52.36 ± 1.38 µg/mL. Compound 1 showed significant cytotoxicity against A2780, PC-3, and MBA-MD-231 cell lines with respective IC50 values of 3.20, 10.68, and 16.30 µM, and the cytotoxicity against A2780 cells was even higher than that of cisplatin (CDDP). With an IC50 value of 10.13 µM, compound 2 also exhibited cytotoxicity against A2780. The in vitro results showed that compound 1 inhibited A2780 cell proliferation, induced apoptosis, and arrested the cell cycle at the S-phase in a concentration-dependent manner.

A new alkaloid derivative from the saprophytic fungus Neohelicomyces hyalosporus PF11-1.

A new alkaloid, neohelicomyine A (1), along with two known alkaloids (2-3), were isolated from the fermentation of Neohelicomyces hyalosporus PF11-1. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1 D and 2 D NMR, HRESIMS and ECD. The bioactivities of all compounds were evaluated using cellular assays, and compounds 2 and 3 displayed moderate cytotoxicities against human cancer (A549, TCA, RD) cells with IC50 values of 26-87 µg/mL.

Morphological and Phylogenetic Analyses Reveal Five New Species in Chaetosphaeriaceae.

Chaetosphaeriaceae is a genera-rich and highly diverse group of fungi with a worldwide distribution in terrestrial and aquatic habitats. Eight fresh collections of Chaetosphaeriaceae were obtained during investigations of hyaline-spored hyphomycetes in China and Thailand. Based on morphological characteristics and phylogenetic analysis of a combined LSU and ITS sequence dataset, Chaetosphaeria obovoidea, Codinaea aseptata, Codinaeella hyalina, Dictyochaeta guizhouensis and Paragaeumannomyces guttulatus were introduced as new species, Codinaea terminalis was reported as new host record, and Codinaea dwaya and Phialosporostilbe scutiformis were introduced as new collections. Phylogenetic analysis in this study revealed that Chaetosphaeria was polyphyletic. Detailed descriptions and illustrations of new taxa and identified species are provided, as well as an updated phylogenetic tree to confirm the placements of these eight new collections.

New species and records of Neomassaria, Oxydothis and Roussoella (Pezizomycotina, Ascomycota) associated with palm and bamboo from China.

Several micro fungi were gathered from bamboo and palm in Guizhou Province, China. In morphology, these taxa resemble Neomassaria, Roussoella and Oxydothis. Multi-gene phylogenetic analyses based on combined ITS, LSU, SSU, rpb2 and tef1 loci confirmed that two are new geographical records for China, (viz. Roussoellasiamensis, Neomassariafabacearum), while two of them are new to science (viz. Oxydothisfortunei sp. nov. and Roussoellabambusarum sp. nov.). The stromata of Roussoellabambusarum are similar to those of R.thailandica, but its ascospores are larger. In addition, multi-gene phylogenetic analyses show that Oxydothisfortunei is closely related to O.inaequalis, but the J- ascus subapical ring as well as the ascospores of O.inaequalis are smaller. Morphological descriptions and illustrations of all species are provided.

[Screening and taxonomic identification of endophytic fungi with antitumor and antioxidant activities from Artemisia lactiflora].

Artemisia lactiflora is an important medicinal plant in China. The antitumor and antioxidant activities of the extracts of 54 endophytic fungi from the plant were screened via MTT assay and DPPH scavenging radical assay, respectively. The bioactive strains were identified based on similarity of 5.8S gene and internal transcribed spacer (ITS) sequences. The results showed that extracts from ten (18.5%) isolates exhibited antitumor activity, and which from two (3.7%) isolates exhibited antioxidant activity. The Alternaria sp. GYBH47 strain was simultaneously having antagonistic activity against HL-60 leukemia, MCF-7 breast and COLO205 colon cell lines, and Phomopsis sp. GYBH42 strain having cytotoxic and antioxidant activities. The results indicated that endophytic fungi from Artemisia lactiflora are potential resources to find valuable bioactive components.