Marine Fungi-Derived Secondary Metabolites: Potential as Future Drugs for Health Care
Hafiz Ansar Rasul Suleria, Megh R. Goyal in Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
An alkaloid gliotoxin (image 37 in Figure 8.3) was isolated from the marine fungus (Aspergillus sp.) that was obtained from the marine sediment collected from an Indian ocean from the depth of 4530 m. The compound (37) was isolated by liquid rotary fermentation based on OSMAC technique to get different compounds; and it was evaluated for pharmacological activities, such as anti-tubercular, antibacterial, and cytotoxic. The compound (37) displayed potent anti-tubercular activity against Mycobacterium Tuberculosis with MIC50 value of 0.030 μM. Moreover, the anti-tubercular efficacy in terms of inhibition was superior to positive control INH suggesting that Sulphur-bridge may improve the efficacy. The compound (37) also exhibited significant selective in vitrocytotoxicity against A549, K562, and Huh-7 cell lines with IC50 values of 0.015, 0.191, and 95.4 μM, respectively. Additionally, deep-sea-derived fungus Aspergillus sp. SCSIO Ind09F01 exhibited moderate antibacterial activity against Gram-positive and Gram-negative microorganisms, such as S. aureus, E. coli and Salmonella [37].
Aspergillosis and Mucormycosis
Rebecca A. Cox in Immunology of the Fungal Diseases, 2020
Several immunomodulating culture supernatants have been identified from A. fumigatus. Gliotoxin appears to be a potent immunosuppressive agent in vitro with action on macrophages and antigen-presenting cells. Gliotoxin inhibits phagocytosis of peritoneal macrophages in a serum-free medium.148,149 In addition, spleen cells and peritoneal macrophages, when treated with gliotoxin, lose their ability to induce alloreactive-cytotoxic T cells. Macromolecular synthesis in T and B lymphoblasts and cell proliferation appear unaffected by gliotoxin. A substance that inhibits the opsonization of fungal cells by normal human serum has also been found in supernatants from A. fumigatus and A. flavus.150 This substance interferes with complement (C3b)-dependent monocyte phagocytosis of fungal conidia and appears to either inhibit activation of the alternative complement pathway or interfere with uptake of C3b onto fungi.150 There was no effect on monocytes alone that were preincubated in the complement-inhibitory factor, suggesting that monocyte-complement receptors were not affected. The in vivo production of either of these immunosuppressive fungal metabolites could compromise host defense mechanisms and thus lead to exacerbation of aspergillosis in an already compromised host.
ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
The term gliotoxin has a generic and a specific meaning. Generically, it is a term used to describe any agent that destroys selectively GLIAL CELLS. Ethidium bromide, alpha aminoadipic acid (alpha AAA) and fluorocitrate are all agents that have been used experimentally to destroy glial cells. They have been used to examine, for example, the proCesses of DEMYELINATIONand REMYELINATION (see Shields et al., 1999) work that hopefully will have important consequences for understanding disorders such as MULTIPLE SCLEROSIS. However, specifically, gliotoxin refers (rather confusingly) to a particular agent: gliotoxin is a fungal toxin that affects plants and animals. Its main properties appear to be suppression of the IMMUNE SYSTEM and destruction of cells (see Richard, 1997).
Drug discovery strategies for novel leukotriene A4 hydrolase inhibitors
Published in Expert Opinion on Drug Discovery, 2021
Till A Röhn, Shin Numao, Heike Otto, Christian Loesche, Gebhard Thoma
More recently, König et al, published a report that Gliotoxin (21) is an aminopeptidase sparing LTA4H inhibitor while Li et al. published a report that HDAC inhibitors such as molecule (22), were aminopeptidase sparing LTA4H inhibitors [79,80]. In both papers, it was claimed that the molecules interact with LTA4H though the active site Zn2+ion. Unfortunately, neither paper looked at PGP hydrolysis in a simple biochemical assay and therefore, it is not clear if the aminopeptidase activity was truly spared. However, careful biochemical characterization and structural information of these compounds may lead to new opportunities in the search for aminopeptidase sparing LTA4H inhibitors. To this end, the finding by Stsiapanava et al. that LTA4H undergoes a conformational change when binding LTA4 may lead to new allosteric compounds interfering with the movements associated with substrate binding [18].
Improving the rates of Aspergillus detection: an update on current diagnostic strategies
Published in Expert Review of Anti-infective Therapy, 2019
Jeffrey D. Jenks, Helmut J. F. Salzer, Martin Hoenigl
Other approaches for mycological detection of IA include the detection of volatile organic compounds in exhaled air, which may allow for detection of a fungal secondary metabolite signature to diagnose IA [94]. Another proposed blood biomarker is bis(methylthio)gliotoxin. Bis(methylthio)gliotoxin is an inactive derivative of gliotoxin, a fungal secondary metabolite that has attracted great interest due to its high biological activity [95]. Both approaches will require external validation before they can be implemented into clinical routine.
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