Antifungal fatty acids

Undecylenic acid (an antifungal fatty acid) is a weak sensitizer. One case of contact allergy from undecylenic acid in Desenex ointment has been reported (Gelfarb and Leider 1960). 

Scientific reports have identified antifungal fatty acids that can combat fungal infections that affect plants, humans and food sources (Altieri et al., 2009 Thormar, 2011). 

Avis, T. J. Belanger, R. R. (2001). Specificity and mode of action of the antifungal fatty acid cis-9-heptadecenoic acid produced by Pseudozyma flocculosa. AppL Environ. Microb., 7, 956-960. 

Triclosan is a broad-spectrum antibacterial and antifungal agent. It is an ingredient in toothpastes and mouthwashes, detergents, laundry soaps, and cosmetics. It kills germs by interfering with the enzyme necessary for fatty-acid synthesis. 

Lipid transfer peptides and proteins occur in eukaryotic and prokaryotic cells. In vitro they possess the ability to transfer phospholipids between lipid membranes. Plant lipid transfer peptides are unspecific in their substrate selectivity. They bind phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and glycolipids. Some of these peptides have shown antifungal activity in vitro The sequences of lipid transfer proteins and peptides contain 91-95 amino acids, are basic, and have eight cysteine residues forming four disulfide bonds. They do not contain tryptophan residues. About 40% of the sequence adopts a helical structure with helices linked via disulfide bonds. The tertiary structure comprises four a-helices. The three-dimensional structure of a lipid transfer peptide from H. vulgare in complex with palmitate has been solved by NMR. In this structure the fatty acid is caged in a hydrophobic cavity formed by the helices. 

Dellar, J.E. Cole, M.D. Waterman, P.G. (1996) Antifungal polyoxygenated fatty acids from Aeollanthus parvifolius. J. Chem. Ecol., 22, 897-906. 

The polyketides are a large family of bio synthetically related NPs, some of which have very great pharmaceutical value (polyketide sales total about 10 billion annually, see also Chapter 7). Some antibiotics (erythromycin, monensin, rifamycin), immunosuppressants (rapamycin), antifungal substances (amphotericin), antiparasitic (aver-mectin) and anticancer drugs (doxorubicin) are polyketides. The term polyketide refers to the fact that the basic carbon skeleton is not a simple hydrocarbon chain as in the case of fatty acids but is a series of linked keto groups in sequence (Figure 3.6). The first phase of this pathway, the generation of carbon skeleton diversification. 

The antifungal properties of fatty acids and several of their derivatives such as amides and methyl esters have been reviewed (113) as have their antimicrobial activities (114). Monolaurin (the ester of 1 auric acid and glycerol) is the most potent lipid derivative tested to date with regard to antibiotic activity. 

Antifungal Terconazole Terazol 3 Triglycerides of fatty acids... 

Materials that induce cationic or positive charges to retard growth of bacteria and fungi have been identified for decades and some have been applied for centuries. Caprylic fatty acid is known for its antifungal activity for processing food products (Hilgren and Salverda 2000), but its antibacterial/antifungal activity from an emulsion has not been reported in the literature or patent office. These emulsions are inexpensive,... 

The main components of this layer are generally long-chain aliphatic hydrocarbons and fatty acids, as well as smaller amounts of methyl esters, long-chain aliphatic alcohols and aldehydes, glycerides, and cholesterol. Similar compounds are present on the web and spider cuticle. It has been established that these compounds may be responsible for the antifungal and antibacterial properties of silk and also play a role in communication. 

Schwartz and co-workers, also at Merck, reported the isolation and elucidation of the structure of pramanicin (12) and a related fatty acid that were discovered during a search for novel antifungal agents.60 The authors reported using a 500 MHz 3 mm micro-inverse probe for the acquisition of the heteronuclear 2D-NMR data to characterize the molecule, including a HMQC spectrum. 

The involvement of desaturase-type enzymes in the biosynthesis of some important lipidic antifeedants now has been firmly established (Fig. Ic) (7). An instructive example of this phenomenon is the production of ricinoleate (a purgative) by a desaturase homolog found in the castor plant. Here, a subtle variation in mechanistic pathway is responsible for the introduction of a C-12 hydroxyl group rather than a 12,13-double bond (7). Another interesting case features the putative dehydrogenation of a cyclopropyl fatty acid to produce sterculate, a potent inhibitor of the mammalian but not the plant A desaturase (8). Finally, the biosynthesis of polyacetylenes with antifungal properties such as falcarindiol is thought to involve a sequence of unique desaturase-mediated oxidations (9). 

When a transcriptional repressor recruits a HD AC to a gene promoter, the HDAC de-acetylates proximal histones, a process which is thought to enhance chromosomal condensation and thereby reduce the ability of transcriptional activators to bind the promoter (14). The observation that chromatin condensation correlates with histone deacetylation was possible only by using small molecule HDAC inhibitors (85). The HDAC inhibitor activity of the short chain fatty acid sodium butyrate was identihed and led to the suggestion that histone acetylation increases DNA accessibility for TFs and the transcriptional machinery (85). The hydroxamic acid containing natural product Trichostatin A (TSA) was a known antifungal agent for 14 years before it was determined to be a potent inhibitor of HDACs... 

Adults have an acidic, fatty substance in and on the skin called sebum. Sebum functions as a natural antifungal agent, put of the innate immune system. Fatty acids have been iitetl for years with the idea that if a substance similar to sebum could be applied to the infected area, the effect of the sebum would be augmented and fungi could be eradi-caicd. The application of fatty acids or their salts does in fxi have an antifungal effect, albeit a feeble one. 

Strategies based on the Simmons-Smith reaction are presently developed for the synthesis of polycyclopropanes of defined absolute and relative stereochemistry in relation with natural product 10, a fascinating natural fatty-acid amide nucleoside that shows promise as an antifungal drug [35, 37],... 

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