Chromatographic analysis of a crude ethyl acetate (EtOAc) extract derived from a solid rice culture incubated at 40°C to mimic the natural ecological niche of the extremophilic fungus
Botryotrichum ...piluliferum
strain WESH19 yielded a new natural butenolide compound (
1
) together with three known metabolites (
2–4
). Chemical structures of the isolated metabolites were confirmed by HR-ESI-MS along with 1D and 2D NMR spectroscopic analyses. Compounds
1–3
revealed pronounced antimicrobial activities against
Staphylococcus aureus
(ATCC 700699),
Enterococcus faecalis
(ATCC 29212), and
Enterococcus faecium
(ATCC 35667), while their antifungal activities were assessed against the extremophilic fungus
Penicillium simplicissimum
strain WSH17 (GenBank Acc. No. MN055685). This study adds another example of how extreme environmental conditions may influence secondary metabolism of the inhabiting fungi.
Cancer is one of the leading causes of death worldwide, accounting for nearly 10 million deaths in 2020. Current treatment methods include hormone therapy, γ-radiation, immunotherapy, and ...chemotherapy. Although chemotherapy is the most effective treatment, there are major obstacles posed by resistance mechanisms of cancer cells and side-effects of the drugs, thus the search for novel anti-cancer compounds, especially from natural sources, is crucial for cancer pharmaceutics research. One natural source worthy of investigation is fungal species. In this study, the cytotoxicity of 5 metabolic compounds isolated from filamentous fungus Aspergillus Carneus. Arugosin C, Averufin, Averufanin, Nidurifin and Versicolorin C were analyzed using NCI-SRB assay on 10 different cell lines of breast cancer, ovarian cancer, glioblastoma and non-tumorigenic cell lines. Averufanin showed highest cytotoxicity with lowest IC
concentrations especially on breast cancer cells. Therefore, Averufanin was further investigated to enlighten cell death and molecular mechanisms of action involved. Cell cycle analysis showed increase in SubG1 phase suggesting apoptosis induction which was further confirmed by Annexin V and Caspase 3/7 Assays. H2A.X staining revealed accumulation of DNA damage in cells treated with Averufanin and finally western blot analysis validated DNA damage response and downstream effects of Averufanin treatment in various signaling pathways. Consequently, this study shows that Averufanin compound induces cell cycle arrest and cell death via apoptosis through causing DNA damage and can be contemplated and further explored as a new therapeutic strategy in breast cancer.
Co-cultivation of the endophytic fungus
with
on solid rice medium led to the production of four new naphthoquinone dimers, fusatricinones A-D (1-4), and a new lateropyrone derivative, ...dihydrolateropyrone (5), that were not detected in axenic fungal controls. In addition, four known cryptic compounds, zearalenone (7), (-)-citreoisocoumarin (8), macrocarpon C (9) and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (10), that were likewise undetectable in extracts from fungal controls, were obtained from the co-culture extracts. The known antibiotically active compound lateropyrone (6), the depsipeptides enniatins B (11), B1 (12) and A1 (13), and the lipopeptide fusaristatin A (14), that were present in axenic fungal controls and in co-culture extracts, were upregulated in the latter. The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The relative and absolute configuration of dihydrolateropyrone (5) was elucidated by TDDFT-ECD calculations.
Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that ...the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above.
This review summarizes the new and/or bioactive compounds reported from deepsea- derived fungi in the last six years (2010 - October 2016) and critically evaluates whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities.
Endophytic fungi including black aspergilli have the potential to synthesize multiple bioactive secondary metabolites. Therefore, the search for active metabolites from endophytic fungi against ...pathogenic microbes has become a necessity for alternative and promising strategies. In this study, 25 endophytic fungal isolates associated with Malus domestica were isolated, grown, and fermented on a solid rice medium. Subsequently, their ethyl acetate crude extracts were pretested for biological activity. One endophytic fungal isolate demonstrated the highest activity and was chosen for further investigation. Based on its phenotypic, ITS ribosomal gene sequences, and phylogenetic characterization, this isolate was identified as Aspergillus tubingensis strain AN103 with the accession number (KR184138). Chemical investigations of its fermented cultures yielded four compounds: Pyranonigrin A (1), Fonsecin (2), TMC 256 A1 (3), and Asperazine (4). Furthermore, 1H-NMR, HPLC, and LC-MS were performed for the identification and structure elucidation of these metabolites. The isolated pure compounds showed moderate-to-potent antibacterial activities against Pseudomonas aeruginosa and Escherichia coli (MIC value ranged from 31 and 121 to 14.5 and 58.3 μg/mL), respectively; in addition, the time−kill kinetics for the highly sensitive bacteria against isolated compounds was also investigated. The antifungal activity results show that (3) and (4) had the maximum effect against Fusarium solani and A. niger with inhibition zones of 16.40 ± 0.55 and 16.20 ± 0.20 mm, respectively, and (2) had the best effect against Candida albicans, with an inhibition zone of 17.8 ± 1.35 mm. Moreover, in a cytotoxicity assay against mouse lymphoma cell line L5178Y, (4) exhibited moderate cytotoxicity (49% inhibition), whereas (1−3) reported weak cytotoxicity (15, 26, and 19% inhibition), respectively. Our results reveal that these compounds might be useful to develop potential cytotoxic and antimicrobial drugs and an alternative source for various medical and pharmaceutical fields.
The endophytic fungus Aspergillus austroafricanus isolated from leaves of the aquatic plant Eichhornia crassipes was fermented axenically on solid rice medium as well as in mixed cultures with ...Bacillus subtilis or with Streptomyces lividans. Chromatographic analysis of EtOAc extract of axenic cultures afforded two new metabolites, namely, the xanthone dimer austradixanthone (1) and the sesquiterpene (+)-austrosene (2), along with five known compounds (3–7). Austradixanthone (1) represents the first highly oxygenated heterodimeric xanthone derivative. When A. austroafricanus was grown in mixed cultures with B. subtilis or with S. lividans, several diphenyl ethers (8–11) including the new austramide (8) were induced up to 29-fold. The structures of new compounds were unambiguously elucidated using 1D- and 2D-NMR spectroscopy, HRESIMS, and chemical derivatization. Compound 7 exhibited weak cytotoxicity against the murine lymphoma L5178Y cell line (EC50 is 12.6 μM). In addition, compounds 9 and 10, which were enhanced in mixed fungal/bacterial cultures, proved to be active against Staphylococcus aureus (ATCC 700699) with minimal inhibitory concentrations (MICs) of 25 μM each (6.6 μg/mL), whereas compound 11 revealed moderate antibacterial activity against B. subtilis 168 trpC2 with an MIC value of 34.8 μM (8 μg/mL).
Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered ...neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.
Fourteen new natural products, namely, 2-(Z)-styryl-5-geranylresorcin-1-carboxylic acid (1), amorfrutin D (2), 4-O-demethylamorfrutin D (3), 8-geranyl-3,5,7-trihydroxyflavanone (4), ...8-geranyl-5,7,3′-trihydroxy-4′-methoxyisoflavone (5), 6-geranyl-5,7,3′-trihydroxy-4′-methoxyisoflavone (6), 8-geranyl-7,3′-dihydroxy-4′-methoxyisoflavone (7), 3-O-demethyldalbinol (8), 6a,12a-dehydro-3-O-demethylamorphigenin (9), (6aR,12aR,5′R)-amorphigenin (10), amorphispironones B and C (11 and 12), resokaempferol 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside-7-O-α-l-rhamnopyranoside (13), and daidzein 7-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (14), together with 40 known compounds, were isolated from the fruits of Amorpha fruticosa. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic analysis as well as from the mass spectrometry data. ECD calculations were performed to determine the absolute configurations of 11 and 15. Compounds 1, 4–6, and 16–23 showed potent to moderate antibacterial activities against several Gram-positive bacteria with MIC values ranging from 3.1 to 100 μM. In addition, compounds 11 and 24–33 were significantly cytotoxic against the L5178Y mouse lymphoma cell line and exhibited IC50 values from 0.2 to 10.2 μM.
The endophytic fungus Penicillium citrinum was isolated from a fresh stem of the Moroccan plant Ceratonia siliqua. Extracts of P. citrinum grown on rice and white bean media yielded five new ...compounds, namely, citriquinochroman (1), tanzawaic acids G and H (2 and 3), 6-methylcurvulinic acid (4), 8-methoxy-3,5-dimethylisoquinolin-6-ol (5), and one new natural product, 1,2,3,11b-tetrahydroquinolactacide (6), which had previously been described as a synthetic compound. In addition, 13 known compounds including seven alkaloids and six polyketides were isolated. The structures of the new compounds were unambiguously determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. Citriquinochroman (1) features a new skeleton, consisting of quinolactacide and (3S)-6-hydroxy-8-methoxy-3,5-dimethylisochroman linked by a C–C bond. 1,2,3,11b-Tetrahydroquinolactacide (6) may be a biogenetic precursor of quinolactacide. Citriquinochroman (1) showed cytotoxicity against the murine lymphoma L5178Y cell line with an IC50 value of 6.1 μM, while the other compounds were inactive (IC50 >10 μM) in this assay.
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Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Aspergillaceae) was performed through various chromatographic workup procedures. The ...achieved results afforded one new natural compound, emericelactone E (1) in addition to known compounds (2–7). The planar structures of the purified compounds were unambiguously carried out using several spectroscopic methods. Both relative and absolute configurations of compound 1 were carefully determined based on NOESY experiments, coupling constants and comparing its optical rotation with related congeners. Moreover, a plausible biosynthetic pathway of 1 and its related derivatives is reported for the first time in our study. The cytotoxic potential of isolated metabolites was assessed toward three human tumor cell lines where some of them exhibited moderate activities compared to paclitaxel as a standard anticancer.
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