Changing patterns of infectious disease

Sordariomycetes is one of the largest classes of Ascomycota that comprises a highly diverse range of fungi characterized mainly by perithecial ascomata and inoperculate unitunicate asci. The class includes many important plant pathogens, as well as endophytes, saprobes, epiphytes, coprophilous and fungicolous, lichenized or lichenicolous taxa. They occur in terrestrial, freshwater and marine habitats worldwide. This paper reviews the 107 families of the class Sordariomycetes and provides a modified backbone tree based on phylogenetic analysis of four combined loci, with a maximum five representative taxa from each family, where available. This paper brings together for the first time, since Barrs’ 1990 Prodromus, descriptions, notes on the history, and plates or illustrations of type or representative taxa of each family, a list of accepted genera, including asexual genera and a key to these taxa of Sordariomycetes. Delineation of taxa is supported where possible by molecular data. The outline is based on literature to the end of 2015 and the Sordariomycetes now comprises six subclasses, 32 orders, 105 families and 1331 genera. The family Obryzaceae and Pleurotremataceae are excluded from the class.

Families of Sordariomycetes

This is a continuation of the papers “Towards a classification of Sordariomycetes” (2015) and “Families of Sordariomycetes” (2016) in which we compile a treatment of the class Sordariomycetes. The present treatment is needed as our knowledge has rapidly increased, from 32 orders, 105 families and 1331 genera in 2016, to 45 orders, 167 families and 1499 genera (with 308 genera incertae sedis) at the time of publication. In this treatment we provide notes on each order, families and short notes on each genus. We provide up-to-date DNA based phylogenies for 45 orders and 163 families. Three new genera and 16 new species are introduced with illustrations and descriptions, while 23 new records and three new species combinations are provided. We also list 308 taxa in Sordariomycetes genera incertae sedis. For each family we provide general descriptions and illustrate the type genus or another genus, the latter where the placement has generally been confirmed with molecular data. Both the sexual and asexual morphs representative of a family are illustrated where available. Notes on ecological and economic considerations are also given.

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Refined families of Sordariomycetes

Cancer is a major cause of death worldwide, with an increasing number of cases being reported annually. The elevated rate of mortality necessitates a global challenge to explore newer sources of anticancer drugs. Recent advancements in cancer treatment involve the discovery and development of new and improved chemotherapeutics derived from natural or synthetic sources. Natural sources offer the potential of finding new structural classes with unique bioactivities for cancer therapy. Endophytic fungi represent a rich source of bioactive metabolites that can be manipulated to produce desirable novel analogs for chemotherapy. This review offers a current and integrative account of clinically used anticancer drugs such as taxol, podophyllotoxin, camptothecin, and vinca alkaloids in terms of their mechanism of action, isolation from endophytic fungi and their characterization, yield obtained, and fungal strain improvement strategies. It also covers recent literature on endophytic fungal metabolites from terrestrial, mangrove, and marine sources as potential anticancer agents and emphasizes the findings for cytotoxic bioactive compounds tested against specific cancer cell lines.

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Endophytic Fungi-Alternative Sources of Cytotoxic Compounds: A Review.

Isatin (1H-indole-2,3-dione) and its derivatives represent an important class of heterocyclic compounds that can be used as precursors for drug synthesis. Since its discovery, a lot of research work has been done regarding the synthesis, chemical properties, and biological and industrial applications of isatin. In this review, we have reported several novel methods for the synthesis of N-, C2-, and C3-substituted and spiro derivatives of isatin. The isatin moiety also shows important chemical reactions such as oxidation, ring expansion, Friedel–Crafts reaction and aldol condensation. These reactions, in turn, produce several biologically viable compounds like 2-oxindoles, tryptanthrin, indirubins, and many more. We have also summarized some recently reported biological activities exhibited by isatin derivatives, like anti-cancer, anti-bacterial, anti-diabetic and others. Special attention has been paid to their anti-cancer activity, and various anti-cancer targets such as histone deacetylase, carbonic anhydrase, tyrosine kinase, and tubulin have been discussed in detail. Other applications of isatin derivatives, such as in the dye industry and in corrosion prevention, have also been discussed.

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Isatin and its derivatives: a survey of recent syntheses, reactions, and applications.

Two new metabolites, an α-pyridone derivative, 3-hydroxy-2-methoxy-5-methylpyridin-2(1H)-one (1), and a ceramide derivative, 3-hydroxy-N-(1-hydroxy-3-methylpentan-2-yl)-5-oxohexanamide (2), and a new natural product, 3-hydroxy-N-(1-hydroxy-4-methylpentan-2-yl)-5-oxohexanamide (3), along with 15 known compounds including chaetoglobosin C (7) and chaetoglobosin F (8) were isolated from the solid culture of the endophytic fungus Botryosphaeria dothidea KJ-1, collected from the stems of white cedar (Melia azedarach L). The structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR experiments and by mass spectrometric measurements), and the structure of 1 was confirmed by X-ray single-crystal diffraction. These metabolites were evaluated in vitro for antimicrobial, antioxidant, and cytotoxicity activities. Pycnophorin (4) significantly inhibited the growth of Bacillus subtilis and Staphyloccocus aureus with equal minimum inhibitory concentration (MIC) values of 25 μM. Stemphyperylenol (5) displayed a potent antifungal activity against the plant pathogen Alternaria solani with MIC of 1.57 μM comparable to the commonly used fungicide carbendazim. Both altenusin (9) and djalonensone (10) showed markedly DPPH radical scavenging activities. In addition, stemphyperylenol (5) and altenuene (6) exhibited strong cytotoxicity against HCT116 cancer cell line with a median inhibitory concentration (IC50) value of 3.13 μM in comparison with the positive control etoposide (IC50 = 2.13 μM). This is the first report of the isolation of these compounds from the endophytic B. dothidea.

Secondary metabolites from the endophytic Botryosphaeria dothidea of Melia azedarach and their antifungal, antibacterial, antioxidant, and cytotoxic activities.

In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, Vb, and C (1-5), in three media. In the present work, five known chaetoglobosins, C, E, F, Fex, and 20-dihydrochaetoglobosin A (5-9), together with the four known compounds (11-14), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (7) with (diethylamino)sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin Fa (10), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds 1, 3-8, and 10 were assayed on radish seedlings; some of these compounds (1, 3, and 6-8) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds 1 and 8-10 showed remarkable cytotoxicity with IC50 values ranging from 3.15 to 8.44 μM, in comparison to the positive drug etoposide (IC50 = 2.13 μM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin Fa (10) displayed a markedly increased cytotoxicity but decreased phytotoxicity.

Chaetoglobosins from Chaetomium globosum, an endophytic fungus in Ginkgo biloba, and their phytotoxic and cytotoxic activities

Antifungal and antibacterial metabolites from an endophytic Aspergillus sp. associated with Melia azedarach

On the basis of the OSMAC (one strain-many compounds) strategy, 14 indole diketopiperazine (DKP) alkaloids, including spirotryprostatins (1-3), tryprostatins (4-6), and cyclotryprostatins (7-14), were isolated from the endophyte Aspergillus fumigatus associated with Melia azedarach L. Their structures were identified by nuclear magnetic resonance and electrospray ionization mass spectrometry data. All the indole DKPs were evaluated for plant growth regulation using the lettuce (Lactuca sativa) seedling growth bioassay, which showed the plant growth influence of the seedling. Among these compounds tested, a tryprostatin-type compound, brevianamide F (6), was identified as a new type of natural potential plant growth inhibitor with a response index (RI) higher than that of the positive control glyphosate, a broad-spectrum systemic herbicide. 6 can also inhibit turnip (Raphanus sativus) shoot and root elongation with RIs of -0.76 and -0.70, respectively, at 120 ppm, and it strongly inhibits amaranth (Amaranthus mangostanus) seedling growth with a high RI of -0.9 at 40 ppm. The structure-allelopathic activity relationship analysis of these isolated alkaloids indicates that tryprostatin-type alkaloids without the C5 prenyl and methoxy group give the most potent inhibition of seedling growth. Brevianamide F (6) could be used to develop a natural eco-friendly herbicide.

Potential Allelopathic Indole Diketopiperazines Produced by the Plant Endophytic Aspergillus fumigatus Using the One Strain–Many Compounds Method

With environmental pollution, residual hazards accumulate and severe drug resistance and many other problems appear; some highly toxic drugs have been banned, and antifungal agents are far from satisfactory. Natural products play an important role in the discovery and development of new pesticides. The natural product griseofulvin (1) has been known as an antifungal agent in the treatment of dermatomycoses for decades. In this study, a series of new griseofulvin derivatives were synthesized with good yields. Their structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry (electrospray ionization). The antifungal activities of griseofulvin analogues were first evaluated against five phytopathogenic fungi ( Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) in vitro. Of significance is that most of them showed excellent antifungal activities against C. gloeosporioides. The antifungal activities of the four best compounds (6a, 6c, 6e, and 6f) against C. gloeosporioides were further investigated in vivo using infected apples. The results suggested that compounds 6c, 6e, and 6f [half-maximal inhibitory concentration (IC50) = 47.25 ± 1.46, 49.44 ± 1.50, and 53.63 ± 1.74 μg/mL, respectively] were better than thiophanate-methyl (IC50 = 69.66 ± 6.07 μg/mL). Furthermore, comparative molecular field analysis was performed on the basis of the antifungal activity results of all 22 of the compounds against C. gloeosporioides in vitro. The three-dimensional coefficient contour plots revealed that the suitable bulky and electronegative acyl-substituted groups seem to be more favorable for increasing activity at the 4' position of griseofulvin. The structure-activity relationships were also discussed. Griseofulvin derivatives can be used for the development of highly effective and safe agricultural fungicides.

Antifungal Activity of Griseofulvin Derivatives against Phytopathogenic Fungi in Vitro and in Vivo and Three-Dimensional Quantitative Structure-Activity Relationship Analysis.

Yu-Qi Gao

Papers

Secondary metabolites from the endophytic Botryosphaeria dothidea of Melia azedarach and their antifungal, antibacterial, antioxidant, and cytotoxic activities.

Chaetoglobosins from Chaetomium globosum, an endophytic fungus in Ginkgo biloba, and their phytotoxic and cytotoxic activities

Antifungal and antibacterial metabolites from an endophytic Aspergillus sp. associated with Melia azedarach

Potential Allelopathic Indole Diketopiperazines Produced by the Plant Endophytic Aspergillus fumigatus Using the One Strain–Many Compounds Method

Antifungal Activity of Griseofulvin Derivatives against Phytopathogenic Fungi in Vitro and in Vivo and Three-Dimensional Quantitative Structure-Activity Relationship Analysis.