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History of antifungals
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Emily L. Larkin, Ali Abdul Lattif Ali, Kim Swindell
Anidulafungin is a derivative of a naturally occurring candin, echinocandin B, produced by Aspergillus nidulans or A. rugulosis [83]. Cilofungin was the first semisynthetic derivative of echinocandin B to be evaluated in clinical trials; however, the trials were discontinued due to associated nephrotoxicity. Further structure modification of cilofungin led to the synthesis of anidulafungin [83].
Anidulafungin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Anidulafungin (VER002, LY-303366; see Figure 148.1) is a semisynthetic echinocandin with broad antifungal activity against pathogenic yeasts and molds. The echinocandins were originally discovered as metabolic by-products of the fermentation process during screening programs for novel antibiotics. Anidulafungin is a derivative of the fermentation metabolite, echinocandin B0, produced by Aspergillus nidulans. The lead compound for anidulafungin was discovered in the 1970s (Benz et al., 1974) and developed at Eli Lily. The drug underwent clinical development at Vicuron Pharmaceuticals and received regulatory approval in 2006. Anidulafungin is now marketed under the brands Eraxis and Ecalta by Pfizer in the United States and Europe, respectively.
Echinocandins – structure, mechanism of action and use in antifungal therapy
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mateusz Szymański, Sandra Chmielewska, Urszula Czyżewska, Marta Malinowska, Adam Tylicki
Echinocandin B (Figure 2) is a major lipopeptide antifungal antibiotic from a complex produced by Aspergillus nidulans and Aspergillus rugulosus. It contains a linoleic acid side chain and a hexacyclic peptide core built by various amino acid residues such as 3,4-dihydroxyhomotyrosine, 3-hydroxy-4-methylproline, 4,5-dihydroxyornithine, 4-hydroxyproline and two threonine residues24. These amino acid residues have a significant effect on antifungal activity and determine the physicochemical properties of the echinocandin B nucleus. For example, modified proline and homotyrosine residues are essential for the antifungal efficacy of echinocandins25. Hydroxyl groups at the three amino acid residues forming the cyclic lipopeptide core, improve the solubility of the drug in water and aid its stability in solutions12. Taking this into account, during the synthesis of newer echinocandin B derivatives, the core was kept unchanged or underwent minor modifications26 (Figure 1). The hydrophobic fatty acid chain attached to the echinocandin B core is crucial for antifungal activity because it acts as a "hook" that allows the drug to anchor in the fungal cell membrane12.