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A set of six systemic clinical azoles [sterol 14<jats:italic>\u03b1<\/jats:italic>-demethylase (CYP51) inhibitors] represents the first-line antifungal treatment. All these drugs were discovered empirically, by monitoring their effects on fungal cell growth, though it had been proven that they kill fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of 14<jats:italic>\u03b1<\/jats:italic>-demethylation of the sterol nucleus. This review briefs the history of antifungal azoles, outlines the situation with the current clinical azole-based drugs, describes the attempts of their repurposing for treatment of human infections with the protozoan parasites that, similar to fungi, also produce endogenous sterols, and discusses the most recently acquired knowledge on the CYP51 structure\/function and inhibition. It is our belief that this information should be helpful in shifting from the traditional phenotypic screening to the actual target-driven drug discovery paradigm, which will rationalize and substantially accelerate the development of new, more efficient and pathogen-oriented CYP51 inhibitors.<\/jats:p>","DOI":"10.1017\/s0031182018000562","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T05:23:53Z","timestamp":1523510633000},"page":"1820-1836","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":118,"title":["CYP51 as drug targets for fungi and protozoan parasites: past, present and future"],"prefix":"10.1017","volume":"145","author":[{"given":"Galina I.","family":"Lepesheva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Friggeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Waterman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2018,4,12]]},"reference":[{"key":"S0031182018000562_ref163","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/26.4.561"},{"key":"S0031182018000562_ref1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.12.2910"},{"key":"S0031182018000562_ref61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.237099"},{"key":"S0031182018000562_ref179","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0021-9258(17)43458-2","article-title":"Yeast cytochrome P-450 catalyzing lanosterol 14 alpha-demethylation. 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