Fungal diseases have been underestimated worldwide but constitute a substantial threat to several plant and animal species as well as to public health. The increase in the global population has entailed an increase in the demand for agriculture in recent decades. Accordingly, there has been worldwide pressure to find means to improve the quality and productivity of agricultural crops. Antifungal agents have been widely used as an alternative for managing fungal diseases affecting several crops. However, the unregulated use of antifungals can jeopardize public health. Application of fungicides in agriculture should be under strict regulation to ensure the toxicological safety of commercialized foods. This review discusses the use of antifungals in agriculture worldwide, the need to develop new antifungals, and improvement of regulations regarding antifungal use.

Antifungal Agents in Agriculture: Friends and Foes of Public Health

/pdf/a-worldwide-list-of-endophytic-fungi-with-notes-on-ecology-4cn4gi8bij.pdf

A worldwide list of endophytic fungi with notes on ecology and diversity.

Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.

https://www.mdpi.com/1422-0067/22/2/959/pdf

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study.

Fungal phytotoxic secondary metabolites are poisonous substances to plants produced by fungi through naturally occurring biochemical reactions. These metabolites exhibit a high level of diversity in their properties, such as structures, phytotoxic activities, and modes of toxicity. They are mainly isolated from phytopathogenic fungal species in the genera of Alternaria, Botrytis, Colletotrichum, Fusarium, Helminthosporium, and Phoma. Phytotoxins are either host specific or non-host specific phytotoxins. Up to now, at least 545 fungal phytotoxic secondary metabolites, including 207 polyketides, 46 phenols and phenolic acids, 135 terpenoids, 146 nitrogen-containing metabolites, and 11 others, have been reported. Among them, aromatic polyketides and sesquiterpenoids are the main phytotoxic compounds. This review summarizes their chemical structures, sources, and phytotoxic activities. We also discuss their phytotoxic mechanisms and structure–activity relationships to lay the foundation for the future development and application of these promising metabolites as herbicides.

Phytotoxic Secondary Metabolites from Fungi

Proc Amer Assoc Cancer Res, Volume 47, 2006

4858 

The cytosolic thioredoxin (Trx) redox system comprising Trx-1 and Trx-1 reductase (TR) which catalyses the NADPH dependent reduction of Trx-1, regulates cell growth and survival. Trx-1, together with peroxiredoxin-1, is an antioxidant that scavenges H2O2. Trx-1 also reduces protein oxidized cysteine residues to regulates the activity of transcription factors including p53, HIF-1α, Sp1 and Nrf2, and to inhibit the activity of the apoptosis inducing proteins Ask-1 and PTEN. Trx-1 is overexpressed in many human tumors where it is associated with increased cell proliferation, decreased apoptosis and poor patient survival. TR provides an ideal target to regulate the activity of overexpressed Trx-1. We have identified the naphthoquinone spiroketal fungal metabolite palmarumycin CP1 as a potent inhibitor of TR in cells but attempts to exploit the activity of CP1 analogs as antitumor agents in vivo have been hampered by their insolubilityA. We have recently developed a series of water soluble CP1 analog prodrugsB the most active being PX-916 with a water solubility of 10 mg/ml and an IC50 for TR of 0.28 μM, which is similar to that of CP1 and the CP1-analog PX-960 to which PX-916 is converted at pH 7.0 (t1/2 = 1 hr) and in plasma (t1/2 100 fold selectivity for TR compared to NADPH dependent human glutathione reductase and cytochrome P-450 reductase. The IC50 for inhibition of MCF-7 breast cancer cell TR by PX-916 was 0.25 μM and the IC50 for growth inhibition 3.1 μM. PX-916 was stable (t1/2 = 37 hr) at pH 4.0 which was used for iv administration to mice. A single iv dose of PX-916 of 25 mg/kg inhibited MCF-7 tumor xenograft TR up to 60% at 24 hr and the inhibition was maintained for at least 48 hr. The growth of MCF-7 tumor xenografts was decreased from 140 mm3/day in the vehicle control to 15 mm3/day 5 days after the end of dosing by PX-916 at 27.5 mg/kg iv daily for 5 doses (89 % decrease, p < 0.05) and to 10 mm3/day by PX-916 at 27.5 mg/kg iv every other day for 5 doses (93 % decrease, p < 0.05). A-673 rhabdomyosarcoma and SHP-77 small cell lung cancer xenografts also showed marked growth inhibition with PX-916 given at 25 to 30 mg/kg iv or ip daily for 5 days. The major toxicities observed 24 hr after the last off 5 daily doses of PX-916 of 25 mg/kg were neutropenia and thrombocytopenia, with no increase in plasma liver enzymes and no significant weight loss. Thus, the studies demonstrate that TR offers a good target for cancer drug discovery and that water soluble palmarumycin analogs inhibit tumor TR and can give excellent tumor growth control. A Wipf et al. Org. Biomol. Chem. 2004, 2 , 1651-1658. B Wipf et al. Org. Biomol. Chem. 2005 , 3 , 3880-3882.

Molecular pharmacology and antitumor activity of palmarumycin based inhibitors of thioredoxin reductase

Modulation of polyketide biosynthetic pathway of the endophytic fungus, Anteaglonium sp. FL0768, by copper (II) and anacardic acid.

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Modulation of polyketide biosynthetic pathway of the endophytic fungus, Anteaglonium sp. FL0768, by copper (II) and anacardic acid.