Metabolites antifungal activity

Pacciaroni AV, Gette ML, Derita M, Ariza-Espinar L, Gil RR, Zacchino SA, Silva GL. (2008) Antifungal activity of Heterothalamus alienus metabolites. 

Prior to excretion, terbinafine is extensively metabolized. No metabolites have been identified that have antifungal activity similar to terbinafine. Approximately 70% of the administered dose is eliminated in the urine. 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Six-membered rings containing three or more heteroatoms do not occur widely in Nature. The 1,2,4-dithiazine ring occurs in the epidithiodioxopiperazine system (257), which is common to a number of fungal metabolites, such as gliotoxin (258), and appears to be the site of the potent antiviral, antibacterial and antifungal activities of these compounds. However, the compounds are probably better considered as diketopiperazines rather than... 

More recently, two new isonakafiiran-type sesquiterpenes were isolated from this sponge species [74], These types of compounds possess interesting antitumor and antifungal activity, and attempts to synthesize them are being conducted [75], Other bioactive metabolites, such as antifouling sesquiterpenes, have also been recently isolated from Dysidea herbacea [76],... 

The most active metabolite was the novel cyclic undecapeptide, cyclosporin A (Figure 8). As an antibiotic, cyclosporin A exhibited only a very narrow spectrum of modest antifungal activity, but in 1972 its true potential was realised. Jean Borel and colleagues at Sandoz discovered that cyclosporin A also neutralised cytotoxic T-cell activity in vitro and prevented haemagglutination in mice immunised against sheep erythrocytes. Further studies revealed that cyclosporin A inhibits T-cell proliferation by blocking the synthesis of IL-2. ... 

Other secondary metabolites from the genus have been reported to possess various biological properties. For example, the components responsible for the antifungic activity of some species from the genus was proven to be polyacetylenes and the antiulcerogenic activity of this genus is associated with polysaccharides. 

The genera Trichoderma and Gliocladium, anamorphs of Hypocrea, have been perhaps the most studied of the fungal organisms which show potential as BCAs. From early investigations of the metabolites produced, a number of simple resorcinols, /7-benzoquinones and anthraquinones were characterised and shown to have antifungal activity. This work will not be considered here since it has been comprehensively reviewed previously [72]. 

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