Two new usnic acid derivatives from the endophytic fungus Mycosphaerella sp (original) (raw)
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Endophytic fungal compounds active against Cryptococcus neoformans and C. gattii
The Journal of antibiotics, 2015
Infections with Cryptococcus are invasive mycoses associated with significant morbidity and mortality, mainly in immunosuppressed patients. Several drugs have been introduced to combat these opportunistic infections. However, resistance of this organism to antifungal drugs has increased, causing difficulties in the treatment. The goal of this work was to evaluate the antifungal activity of ethanol extracts from endophytic fungi isolated from plants collected from different Brazilian ecosystems and to perform the fractionation of the most promising extract. Four-hundred fungal extracts were investigated by microdilution broth assays against Cryptococcus neoformans and Cryptococcus gattii at a concentration of 500 μg ml − 1 . Among them, the extract of Mycosphaerella sp. UFMGCB 2032, an endophytic fungus isolated from the plant Eugenia bimarginata DC. (Myrtaceae) exhibited outstanding antifungal activity against C. neoformans and C. gattii, with MIC values of 31.2 μg ml − 1 and 7.8 μg ml − 1 , respectively. The fractionation of this extract using liquid-liquid partitioning and semi-preparative HPLC afforded two eicosanoic acids with antifungal activity, compound 1, (2 S,3 R,4 R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14oxoeicos-6,12-dienoic acid with MIC values ranging from 1.3-2.50 μg ml − 1 , and compound 2, known as myriocin, with MIC values of 0.5 μg ml − 1 against C. neoformans and C. gattii. These compounds are reported for the first time in the Mycosphaerella genus.
Microbial Pathogenesis, 2016
The antifungal effects of two eicosanoic acids, 2-amino-3,4-dihydroxy-2-25-(hydroxymethyl)-14-oxo-6,12-eicosenoic acid (compound 1) and myriocin (compound 2), isolated from Mycosphaerella sp. were evaluated against Cryptococcus neoformans and C. gattii. The compounds displayed antifungal activities against several isolates of C. neoformans and C. gattii, with minimal inhibitory concentration (MIC) values ranging from 0.49 to 7.82 mM for compound 1 and 0.48e1.95 mM for compound 2. In the checkerboard microtiter test, both compounds exhibited synergistic activity with amphotericin B against C. gattii. Ultrastructural analysis revealed several signs of damage in C. gattii and C. neoformans cells treated with compounds 1 and 2, including deformities in cell shape, depressions on the surface, and withered cells. The cells of C. gattii treated with compounds 1 and 2 showed less loss of cellular material in comparison to those treated with amphotericin B. The difference in cellular material loss increased in a test compound concentration-dependent manner. Consistent with this observation, compounds 1 and 2 were able to internalize propidium iodide (PI) in C. gattii cells. In addition, compound 2 induced the formation of several pseudohyphae, suggesting that it could reduce virulence in C. gattii cells. The study results show that these natural products led to membrane damage; however, this may not be the main target of action. These compounds have potential antifungal activity and could be useful in further studies for developing more effective combination therapies with amphotericin B and reducing side effects in patients.
Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH 3 at C-2 or the presence of one or two NO 2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up OPEN ACCESS
2012
Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH 3 at C-2 or the presence of one or two NO 2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up
Chemical Constituents of the Fungus Mycoleptodiscus sp. 09F0149
Chemistry of Natural Compounds, 2018
During a program of investigation on potentially bioactive secondary metabolites from Formosan endemic plant endophytes, an endophytic fungal strain, Mycoleptodiscus sp. (Magnaporthaceae) BCRC 09F0149, was isolated from the root of Piper sintenense Hatus. (Piperaceae). Previous chemical investigations of the genus Mycoleptodiscus have received less attention, and only a few articles have been reported [1-3]. In the course of our search for potentially diverse secondary metabolites from natural fungal sources, we have investigated the minor metabolites of the genus Mycoleptodiscus and examined the EtOAc-soluble fraction of Mycoleptodiscus sp. Current phytochemical investigation of the above-mentioned fungus has led to the isolation of seven metabolites, including two known aliphatics, one benzenoid, and four known steroids. The structures of the isolated metabolites were determined by extensive analysis of their spectroscopic data as well as by comparison with literature reports. The chemistry and bioactivity of Mycoleptodiscus sp. 09F0149 have never been studied previously. Among them, compounds 1-7 were isolated for the first time from the genus Mycoleptodiscus.
Fungal endophytes A potential source of antifungal compounds
Frontiers in Bioscience, 2012
Introduction 3. Antifungal compounds produced by endophytic fungi 3.1. Compounds produced by coelomycetes 3.2. Compounds produced by ascomycetes 3.3. Compounds produced by hyphomycetes 3.4. Compounds produced by unidentified fungus 4. Volatile organic compounds from endophytic fungus 5. Outlook 6. Acknowledgment 7. References Colletotrichum gloeosporioides Cryptocarya mandioccana Cis-4-hydroxy-6-deoxyscytalone (64), (4R)-4,8-dihydroxy-alpha-tetralone (65) Exophiala sp. Adenocarpus foliolosus Exochromone (66) Cryptosporiopsis quercina Tripterigeum wilfordii Cryptocandin A (67) Cryptosporiopsis sp. Pinus sylvestris Echinocandins A (68), B (69), D (70), H (71) Pezicula sp. Fagus sylvatica Echinocandins A (68), B (69), D (70), H (71) Cryptosporiopsis quercina Phleum pratense Cryptocin (72) Hormonema sp. (ATCC 74360) Juniperus communis Enfumafungin (73) Epichloe typhina Phleum pratense Epichlicin (74) Edenia gomezpompae Callicarpa acuminata Preussomerin EG1 (75), Preussomerin EG2 (76), Preussomerin EG3 (77) Endophytic strain E99297 Cistus salvifolius 5-(1,3-Butadien-1-yl)-3-(propen-1-yl)-2 (5H)-furanone (78) Botryosphaeria rhodina Bidens pilosa Botryorhodine A (79), B (80), C (81), D (82) Dinemasporium strigosum Calystegia sepium Dinemasone A (83), B (84), C (85) Chaetomium globosum Ginkgo biloba Chaetoglobosin A (86), C (87) Xylaria sp. PSU-D14 Garcinia dulcis Sordaricin (88) Xylaria sp. F0010 Abies holophylla Griseofulvin (89), 7-dechlorogriseofulvin (90) PSU-N24. Garcinia nigrolineata Griseofulvin (89) Xylaria sp. Palicourea marcgravii 2-hexyl-3-methylbutanodioic acid (91), Cytochalasin D (92) Xylaria sp. Ginkgo biloba 7-amino-4-methylcoumarin (93) Penicillium paxilli PSU-A71 Garcinia atroviridis Penicillone (94), Pyrenocine A (95), Pyrenocine B (96) Verticillium sp. Rehmannia glutinosa 2,6-dihydroxy-2-methyl-7-(prop-1E-enyl)-1-benzofuran-3 (2H)-one (97), Massariphenone (98), Ergosterol peroxide (99) Arthrinium phaeospermum Unidentified grass Arthrichitin (100) Nigrospora sp. YB-141 Azadirachta indica Solanapyrone C (101), Solanapyrone N (102), Solanapyrone O (103), Nigrosporalactone (104), Phomalactone (105) Trichoderma harzianum Llexcornuta Lindl Trichodermin (106) Sr. No Fungus Plant Source Compounds isolated Nodulisporium sp. Erica arborea Nodulisporin D (107), E (108), F (109), (3S,4S,5R)-2,4,6-trimethyloct-6-ene-3,5-diol (110), 5-hydroxy-2-hydroxymethyl-4H-chromen-4-one (111), 3-(2,3-dihydroxyphenoxy)-butanoic acid (112), Benzene 1,2,3 triol (113) Aspergillus clavatus and Paecilomyces sp. Taxus mairei and Torreya grandis Brefeldin A (114) Eupenicillium brefeldianum Arisaema erubescens Brefeldin A (114)
Antifungal Activity of extracts from two Ouratea species on Candida albicans
Plants are invaluable sources of pharmaceutical products and Brazil, in particular, has yielded an incredible array of plant and animal products that have drawn the attention of ethnopharmacologists from around the world. Ouratea is a genus of tropical plants within the Ochnaceae. Ouratea is widespread throughtout the tropics, with species in Costa Rica, Brazil, Jamaica, and Kenya. The search for compounds with antimicrobial activity is urgent and indispensable for the treatment of infectious diseases caused by microorganisms resistant to traditional antimicrobial drugs. A screening was conducted with organic extracts from two species, from roots and leaves of Ouratea hexasperma var. planchonii Engl. and leaves and branches of Ouratea parviflora Engl., to identify plant extracts with antifungal properties against Candida albicans. Initially, minimal inhibitory concentrations (MICs) were determined in C. albicans cellular suspension in Sabouraud medium, in a range of 0.060-3.0 mg/ml....
Active antifungal substances from natural sources
2007
The spread of multidrug-resistant strains of fungus and the reduced number of drugs available, makes it necessary to discover new classes of antifungals and compounds that inhibit these resistant mechanisms. This has led to a search for therapeutic alternatives, particularly among medicinal plants and compounds isolated from them used for their empirically antifungal properties. In these natural sources, a series of molecules with antifungal activity against different strains of fungus have been found, which are of great importance to humans and plants.
Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents
Chemical biology & drug design, 2014
New Mannich base-type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4-allyl-2-methoxy-6-(morpholin-4-ylmethyl) phenyl benzoate (7) and 4-{5-allyl-2-[(4-chlorobenzoyl)oxy]-3-methoxybenzyl}morpholin-4-ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and...