{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T23:56:45Z","timestamp":1788134205113,"version":"build-2803163510"},"reference-count":109,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T00:00:00Z","timestamp":1531785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sterol 14\u03b1-demethylase (SDM) is essential for sterol biosynthesis and is the primary molecular target for clinical and agricultural antifungals. SDM has been demonstrated to be a valid drug target for antiprotozoal therapies, and much research has been focused on using SDM inhibitors to treat neglected tropical diseases such as human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis. Sterol C24-methyltransferase (24-SMT) introduces the C24-methyl group of ergosterol and is an enzyme found in pathogenic fungi and protozoa but is absent from animals. This difference in sterol metabolism has the potential to be exploited in the development of selective drugs that specifically target 24-SMT of invasive fungi or protozoa without adversely affecting the human or animal host. The synthesis and biological activity of SDM and 24-SMT inhibitors are reviewed herein.<\/jats:p>","DOI":"10.3390\/molecules23071753","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T08:45:42Z","timestamp":1531903542000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Synthesis and Biological Activity of Sterol 14\u03b1-Demethylase and Sterol C24-Methyltransferase Inhibitors"],"prefix":"10.3390","volume":"23","author":[{"given":"David J.","family":"Leaver","sequence":"first","affiliation":[{"name":"Department of Biology, Geology and Physical Sciences, Sul Ross State University, Alpine, TX 79832, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6423","DOI":"10.1021\/cr200021m","article-title":"Biosynthesis of cholesterol and other sterols","volume":"111","author":"Nes","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1194\/jlr.M054643","article-title":"Discovery of an ergosterol-signaling factor that regulates Trypanosoma brucei growth","volume":"56","author":"Haubrich","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.abb.2010.10.008","article-title":"Purification, characterization and inhibition of sterol C24-methyltransferase from Candida albicans","volume":"505","author":"Ganapathy","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.3390\/molecules14114690","article-title":"Steroidal triterpenes: Design of substrate-based inhibitors of ergosterol and sitosterol synthesis","volume":"14","author":"Liu","year":"2009","journal-title":"Molecules"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.chembiol.2015.08.017","article-title":"Fluorinated sterols are suicide inhibitors of ergosterol biosynthesis and growth in Trypanosoma brucei","volume":"22","author":"Leaver","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.abb.2008.11.003","article-title":"Sterol 24-C-methyltransferase: An enzymatic target for the disruption of ergosterol biosynthesis and homeostasis in Cryptococcus neoformans","volume":"481","author":"Nes","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/infdis\/jiv228","article-title":"VFV as a new effective CYP51 structure-derived drug candidate for chagas disease and visceral leishmaniasis","volume":"212","author":"Lepesheva","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_8","first-page":"502","article-title":"New chemotherapeutic strategies against malaria, leishmaniasis and trypanosomiases","volume":"20","author":"Zucca","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejmech.2017.04.044","article-title":"An overview of azoles targeting sterol 14\u03b1-demethylase for antileishmanial therapy","volume":"135","author":"Emami","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","first-page":"323","article-title":"Targets and patented drugs for chemotherapy of Chagas disease","volume":"Volume 1","author":"Choudhary","year":"2010","journal-title":"Frontiers in Anti-Infective Drug Discovery"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Simarro, P.P., Cecchi, G., Franco, J.R., Paone, M., Diarra, A., Ruiz-Postigo, J.A., F\u0450vre, E.M., Mattioli, R.C., and Jannin, J.G. (2012). Estimating and mapping the population at risk of sleeping sickness. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001859"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.3390\/molecules15064129","article-title":"Conazoles","volume":"15","author":"Heeres","year":"2010","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1517\/13543784.9.3.593","article-title":"Novel triazole antifungal agents","volume":"9","author":"Hoffman","year":"2000","journal-title":"Exp. Opin. Investig. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijpddr.2012.06.001","article-title":"CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds","volume":"2","author":"Hargrove","year":"2012","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3390\/90400185","article-title":"Mechanism-based enzyme inactivators of phytosterol biosynthesis","volume":"9","author":"Zhou","year":"2004","journal-title":"Molecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1128\/AAC.00349-16","article-title":"The investigational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme","volume":"60","author":"Warrilow","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lamberth, C., and Dinges, J. (2012). Sterol biosynthesis inhibiting triazole fungicides. Bioactive Heterocyclic Compound Classes: Agrochemicals, Wiley-VCH Verlag GmbH & Co. KGaA.","DOI":"10.1002\/9783527664412"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1128\/AEM.01332-10","article-title":"Mechanism of binding of prothioconazole to Mycosphaerella graminicola CYP51 differs from that of other azole antifungals","volume":"77","author":"Parker","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1128\/AEM.03965-14","article-title":"Novel substrate specificity and temperature-sensitive activity of Mycosphaerella graminicola CYP51 supported by the native NADPH cytochrome P450 reductase","volume":"81","author":"Price","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/ps.4029","article-title":"Azole fungicides\u2013understanding resistance mechanisms in agricultural fungal pathogens","volume":"71","author":"Price","year":"2015","journal-title":"Pest Manag. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25582","DOI":"10.1074\/jbc.M110.133215","article-title":"Structural insights into inhibition of sterol 14\u03b1-demethylase in the human pathogen Trypanosoma cruzi","volume":"285","author":"Lepesheva","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1021\/jo00003a059","article-title":"Assessment of the active-site requirements of lanosterol 14\u03b1-demethylase: Evaluation of novel substrate analogues as competitive inhibitors","volume":"56","author":"Tuck","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/jm00055a012","article-title":"32-Methyl-32-oxylanosterols: Dual-action inhibitors of cholesterol biosynthesis","volume":"36","author":"Frye","year":"1993","journal-title":"J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1194\/jlr.M021865","article-title":"Structural complex of sterol 14\u03b1-demethylase (CYP51) with 14\u03b1-methylenecyclopropyl-7-24,25-dihydrolanosterol","volume":"53","author":"Hargrove","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9670","DOI":"10.1021\/bi00030a003","article-title":"Substrate-based inhibitors of lanosterol 14\u03b1-methyl demethylase: I. Assessment of inhibitor structure-activity relationship and cholesterol biosynthesis inhibition properties","volume":"34","author":"Trzaskos","year":"1995","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1021\/bi00030a004","article-title":"Substrate-based inhibitors of lanosterol 14\u03b1-methyl demethylase: II. Time-dependent enzyme inactivation by selected oxylanosterol analogs","volume":"34","author":"Trzaskos","year":"1995","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0022-2275(20)41987-X","article-title":"Lanosterol 14\u03b1-demethylase (P45014DM): Effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol","volume":"32","author":"Tuck","year":"1991","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22591","DOI":"10.1016\/S0021-9258(18)41570-0","article-title":"Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase by 14\u03b1-flurolanost-7-en-3-ol","volume":"268","author":"Trzaskos","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1021\/jo00292a037","article-title":"Synthesis of potential mechanism-based inactivators of lanosterol 14\u03b1-methyl demethylase","volume":"55","author":"Frye","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1074\/jbc.M510317200","article-title":"CYP51 from Trypanosoma cruzi: A phyla-specific residue in the B\u2019 helix defines substrate preferences of sterol 14\u03b1-demethylase","volume":"281","author":"Lepesheva","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1021\/jm00194a023","article-title":"Antimycotic imidazoles. Part 4. Synthesis and antifungal activity of ketoconazole, a new potent orally active broad-spectrum antifungal agent","volume":"22","author":"Heeres","year":"1979","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1021\/jm00143a019","article-title":"Antimycotic Imidazoles. 5. Synthesis and antimycotic properties of 1-[[2-aryl-4-(arylalkyl)-1,3-dioxolan-3-yl]methyl]-1H-imidazoles","volume":"24","author":"Heeres","year":"1981","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1021\/jm00358a032","article-title":"Antimycotic azoles. 6. Synthesis and antifungal properties of terconazole, a novel triazole ketal","volume":"26","author":"Heeres","year":"1983","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1021\/jm00373a015","article-title":"Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones","volume":"27","author":"Heeres","year":"1984","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S267","DOI":"10.1093\/clinids\/12.Supplement_3.S267","article-title":"Discovery of fluconazole, a novel antifungal agent","volume":"12","author":"Richardson","year":"1990","journal-title":"Rev. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5657","DOI":"10.1016\/0040-4039(96)01203-8","article-title":"Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals SCH 51048 and SCH 56592","volume":"37","author":"Saksena","year":"1996","journal-title":"Tetrahedron Lett."},{"key":"ref_37","first-page":"180","article-title":"Advances in the chemistry of novel broad-spectrum orally active azole antifungals: Recent studies leading to the discovery of SCH 56592","volume":"198","author":"Saksena","year":"1997","journal-title":"Spec. Publ. R. Soc. Chem."},{"key":"ref_38","first-page":"191","article-title":"Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits","volume":"19","author":"Livni","year":"1992","journal-title":"Nucl. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Korwar, S., Amir, S., Tosso, P.N., Desai, B.K., Kong, C.J., Fadnis, S., Telgang, N.S., Ahmad, S., Roper, T.D., and Gupton, B.F. (2017). The application of a continuous Grignard reaction in the preparation of fluconazole. Eur. J. Org. Chem., 6495\u20136498.","DOI":"10.1002\/ejoc.201701002"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.bmcl.2008.12.026","article-title":"Synthesis and antifungal activity of 1,2,3-triazole containing fluconazole analogues","volume":"19","author":"Aher","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1016\/j.bmcl.2014.05.068","article-title":"Design and optimization of highly-selective fungal CYP51 inhibitors","volume":"24","author":"Hoekstra","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1016\/j.bmcl.2017.06.037","article-title":"Design and optimization of highly-selective, broad spectrum fungal CYP51 inhibitors","volume":"27","author":"Yates","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e00333-17\/1","DOI":"10.1128\/AAC.00333-17","article-title":"The tetrazole VT-1161 is a potent inhibitor of Trichophyton rubrum through its inhibition of T. rubrum CYP51","volume":"61","author":"Warrilow","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6154","DOI":"10.1128\/AEM.01195-14","article-title":"Clotrimazole as a potent agent for treating the oomycete fish pathogen Saprolegnia parasitica through inhibition of sterol 14\u03b1-demethylase (CYP51)","volume":"80","author":"Warrilow","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1016\/j.bmc.2018.02.051","article-title":"Synthesis and fungicidal activity of novel imidazole-based ketene dithioacetals","volume":"26","author":"Gagnepain","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.1021\/acs.jmedchem.8b00641","article-title":"Sterol 14\u03b1-demethylase structure-based design of VNI ((R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) derivatives to target fungal infections: Synthesis, biological evaluation, and crystallographic analysis","volume":"61","author":"Friggeri","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11242","DOI":"10.1021\/cr5003134","article-title":"Drug strategies targeting CYP51 in neglected tropical diseases","volume":"114","author":"Choi","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0022-2275(20)37358-2","article-title":"Sterol synthesis. A simplified method for the synthesis of 32-oxygenated derivatives of 24,25-dihydrolanosterol","volume":"22","author":"Parish","year":"1981","journal-title":"J. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s11745-008-3225-y","article-title":"CYP51: A major drug target in the cytochrome P450 superfamily","volume":"43","author":"Lepesheva","year":"2008","journal-title":"Lipids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0045-2068(76)90011-0","article-title":"Sterol biosynthesis: Establishment of the structure of 3-p-bromobenzoyloxy-5\u03b1-cholest-8(14)-en-15-ol","volume":"5","author":"Phillips","year":"1976","journal-title":"Bioorg. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1039\/C39750000213","article-title":"Synthesis and configuration at C-15 of the epimeric 5-lanost-8-en-3,15-diols","volume":"6","author":"Gibbons","year":"1975","journal-title":"J. Chem. Soc. Chem. Commun."},{"key":"ref_52","unstructured":"Gaylor, J.L., Johnson, P.R., Ko, S.S., Magolda, R.L., Stam, S.H., and Trzaskos, J.M. (1991). Steroid Derivatives Useful as Hypocholesterolemics. (5034548), U.S. Patent."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.2174\/092986712799462621","article-title":"Azole antimycotics\u2014A highway to new drugs or a dead end?","volume":"19","author":"Musiol","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0167-6296(02)00126-1","article-title":"The price of innovation: New estimates of drug development costs","volume":"22","author":"DiMasi","year":"2003","journal-title":"J. Health Econ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/infdis\/jit042","article-title":"VNI cures acute and chronic experimental Chagas disease","volume":"208","author":"Villalta","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/jac\/44.2.283","article-title":"In-vitro comparative activity of UR-9825, itraconazole and fluconazole against clinical isolates of Candida spp.","volume":"44","author":"Ramos","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1128\/AAC.27.5.832","article-title":"Activity of UK-49,858, a bis triazole derivative, against experimental infections with Candida albicans and Trichophyton mentagrophytes","volume":"27","author":"Richardson","year":"1985","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.chembiol.2007.10.011","article-title":"Sterol 14\u03b1-demethylase as a potential target for antitrypanosomal therapy: Enzyme inhibition and parasite cell growth","volume":"14","author":"Lepesheva","year":"2007","journal-title":"Chem. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bettiol, E., Samanovic, M., Murkin, A.S., Raper, J., Buckner, F., and Rodriguez, A. (2009). Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000384"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chen, C., Leung, S.S.F., Guilbert, C., Jacobson, M.P., McKerrow, J.H., and Podust, L.M. (2010). Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000651"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/B978-0-12-385863-4.00004-6","article-title":"Targeting Trypanosoma cruzi sterol 14\u03b1-demethylase (CYP51)","volume":"75","author":"Lepesheva","year":"2011","journal-title":"Adv. Parasitol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJMoa011882","article-title":"Fluconazole for the treatment of cutaneous leishmaniasis caused by Lesihmania major","volume":"346","author":"Alrajhi","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1126\/science.273.5277.969","article-title":"Cure of short- and long term experimental Chagas\u2019 disease using D0870","volume":"273","author":"Urbina","year":"1996","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0924-8579(02)00273-X","article-title":"In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease","volume":"21","author":"Urbina","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10789","DOI":"10.1021\/bi048967t","article-title":"CYP51 from Trypanosoma brucei is obtusifoliol-specific","volume":"43","author":"Lepesheva","year":"2004","journal-title":"Biochemistry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0924-8579(96)00325-1","article-title":"Ultrastructural alterations in Tyrpanosoma (Schizotrypanum) cruzi induced by \u039424(25) sterol methyl transferase inhibitors and their combinations with ketoconazole","volume":"7","author":"Vivas","year":"1996","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1128\/AAC.26.1.5","article-title":"In vitro studies with R 51,211 (Itraconazole)","volume":"26","author":"Shadomy","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/clinids\/9.Supplement_1.S33","article-title":"Degenerative changes in fungi after itraconazole treatment","volume":"9","author":"Borgers","year":"1987","journal-title":"Rev. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1439-0507.2008.01523.x","article-title":"Antifungal agents-clinical pharmacokinetics and drug interactions","volume":"51","author":"Lipp","year":"2008","journal-title":"Mycoses"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/QCO.0b013e3282f1be91","article-title":"Mould-active azoles: Pharmacokinetics, drug interactions in neutropenic patients","volume":"20","author":"Gubbins","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0009-2797(99)00169-6","article-title":"Differential inhibition of human CYP3A4 and Candida albicans CYP51 with azole antifungal agents","volume":"125","author":"Lamb","year":"2000","journal-title":"Chem. Biol. Interact."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0166-6851(89)90026-1","article-title":"Perturbation of sterol biosynthesis by itraconazole and ketoconazole in Leishmania mexicana mexicana infected macrophages","volume":"33","author":"Hart","year":"1989","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1001\/archderm.1996.03890310070009","article-title":"Treatment of cutaneous leishmaniasis with itraconazole. Randomized double-blind study","volume":"132","author":"Momeni","year":"1996","journal-title":"Arch. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1111\/j.1529-8019.2009.01264.x","article-title":"Cutaneous leishmaniasis treated with itraconazole","volume":"22","author":"Baroni","year":"2009","journal-title":"Dermatol. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.tmaid.2006.09.004","article-title":"Cutaneous leishmaniasis treatment","volume":"5","author":"Minodier","year":"2007","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2174\/1381612023396177","article-title":"Chemotherapy of Chagas disease","volume":"8","author":"Urbina","year":"2002","journal-title":"Curr. Pharm. Des."},{"key":"ref_77","unstructured":"J\u00e4ger, T., Koch, O., and Floh\u00e9, L. (2013). Ergosterol biosynthesis for the specific treatment of Chagas disease: From basic science to clinical trials. Trypanosomatid Diseases: Molecular Routes to Drug Discovery, Wiley-VCH Verlag GmbH & Co. KGaA. [1st ed.]."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1021\/jm050691f","article-title":"Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole","volume":"49","author":"Benaim","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"583","DOI":"10.4269\/ajtmh.2010.09-0620","article-title":"Case report: Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus","volume":"82","author":"Pinazo","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/0040-4039(95)00143-Z","article-title":"Highly stereoselective access to novel 2,2,4-trisubstituted tetrahydrofurans by halocyclization: Practical chemoenzymatic synthesis of SCH 51048, a broad-spectrum orally active antifungal agent","volume":"36","author":"Saksena","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_81","unstructured":"Chidambaram, V.S., Miryala, A.K., and Wadhwa, L. (2009). Process for Preparing Posaconazole and Intermediates Thereof. (WO2009141837A2), PCT International Application."},{"key":"ref_82","unstructured":"Charyulu, P.V.R., Gowda, D.J.C., Rajmahendra, S., and Raman, M. (2017). Crystalline Forms of Posaconazole Intermediate and Process for the Preparation of Amorphous Posaconazole. (WO2017051342A1), U.S. PCT International Application."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1074\/jbc.M109.067470","article-title":"Crystal structures of Trypanosoma brucei sterol 14\u03b1-demethylase and implications for selective treatment of human infections","volume":"285","author":"Lepesheva","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1016\/j.tetlet.2017.09.070","article-title":"A convergent, scalable and stereoselective synthesis of azole CYP51 inhibitors","volume":"58","author":"Lepesheva","year":"2017","journal-title":"Tetrahedron Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/0006-291X(91)92021-B","article-title":"Regulation of sterol biosynthesis in sunflower by 24(R,S)25-epiminolanosterol, a novel C-24 methyl transferase inhibitor","volume":"177","author":"Nes","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0003-9861(89)90226-9","article-title":"Metabolism of 24(R,S),25-epiminolanosterol to 25-aminolanosterol and lanosterol by Gibberella fujikuroi","volume":"272","author":"Nes","year":"1989","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6230","DOI":"10.1016\/S0021-9258(18)83338-5","article-title":"Inhibition of cholesterol synthesis and cell growth by 24(R,S),25-iminolanosterol and triparanol in cultured rat hepatoma cells","volume":"264","author":"Popjak","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6290","DOI":"10.1074\/jbc.M511749200","article-title":"Mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in Trypanosoma brucei","volume":"281","author":"Zhou","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1159\/000239458","article-title":"Antiproliferative effects of \u039424(25) sterol methyl transferase inhibitors on Trypanosoma (Schizotrypanum) cruzi: In vitro and in vivo studies","volume":"42","author":"Urbina","year":"1996","journal-title":"Chemotherapy"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1194\/jlr.M079418","article-title":"Sterol methyltransferase a target for anti-amoebatherapy: Towards transition state analog and suicide substrate drug design","volume":"58","author":"Kidane","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/00397918808077348","article-title":"Synthesis of new epiminoisopentenoids","volume":"18","author":"Parish","year":"1998","journal-title":"Synth. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1388-1981(00)00138-4","article-title":"Sterol methyl transferase: Enzymology and inhibition","volume":"1529","author":"Nes","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.bbalip.2010.06.007","article-title":"Cloning, mechanistic and functional analysis of a fungal sterol C24-methyltransferase implicated in brassicasterol biosynthesis","volume":"1801","author":"Pereira","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1194\/jlr.M600404-JLR200","article-title":"Cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of Trypanosoma brucei","volume":"48","author":"Zhou","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1021\/jm00284a013","article-title":"Hypocholesterolemic agents. 8. Synthesis of 25-azadihydrolanosterol and derivatives","volume":"14","author":"Lu","year":"1971","journal-title":"J. Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1021\/bi00311a003","article-title":"Azasterol inhibition of 24-sterol methyltransferase in Saccharomyces cerevisiae","volume":"23","author":"Oehlschlager","year":"1984","journal-title":"Biochemistry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bbalip.2016.12.003","article-title":"24-Methylenecyclopropane steroidal inhibitors: A Trojan horse in ergosterol biosynthesis that prevents growth of Trypanosoma brucei","volume":"1862","author":"Miller","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/S0960-894X(99)00242-5","article-title":"Isolation and characterization of an active-site peptide from a sterol methyl transferase with a mechanism-based inhibitor","volume":"9","author":"Marshall","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1016\/j.phytochem.2009.09.003","article-title":"Cloning, functional expression and phylogenetic analysis of plant sterol 24C-methyltransferases involved in sitosterol biosynthesis","volume":"70","author":"Neelakandan","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.abb.2003.08.029","article-title":"Sterol methyltransferase2: Purification, properties, and inhibition","volume":"420","author":"Zhou","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bmcl.2003.10.015","article-title":"Mechanism-based active site modification of the soybean sterol methyltransferase by 26,27-dehydrocycloartenol","volume":"14","author":"Song","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1080\/00397919608003800","article-title":"Synthesis of rationally designed mechanism-based inactivators of the (S)-adenosyl-L-methionine: \u039424(25)-sterol methyl transferase","volume":"26","author":"Jia","year":"1996","journal-title":"Synth. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s11745-004-1290-7","article-title":"Disruption of ergosterol biosynthesis, growth, and the morphological transition in Candida albicans by sterol methyltransferase inhibitors containing sulfur at C-25 in the sterol side chain","volume":"39","author":"Kanagasabai","year":"2004","journal-title":"Lipids"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1042\/BJ20121818","article-title":"C24-Methylation of 26-fluorocycloartenols by recombinant sterol C24-methyltransferase from soybean: Evidence for channel switching and its phylogenetic implications","volume":"456","author":"Patkar","year":"2013","journal-title":"Biochem. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1039\/c2ob25511a","article-title":"Continuous-flow synthesis of activated vitamin D3 and its analogues","volume":"10","author":"Fuse","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/S0968-0896(00)00177-2","article-title":"Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents","volume":"8","author":"Chung","year":"2000","journal-title":"Bioorg. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/1087057116673796","article-title":"Evaluation of parameters impacting drug susceptibility in intracellular Trypanosoma cruzi assay protocols","volume":"22","author":"Yang","year":"2017","journal-title":"SLAS Discov."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1056\/NEJMoa1313122","article-title":"Randomized trial of posaconazole and benznidazole for chronic Chagas disease","volume":"370","author":"Molina","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.jacc.2016.12.023","article-title":"Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: The stop-Chagas trial","volume":"69","author":"Morillo","year":"2017","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/7\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:12:39Z","timestamp":1760195559000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/7\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,17]]},"references-count":109,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["molecules23071753"],"URL":"https:\/\/doi.org\/10.3390\/molecules23071753","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,17]]}}}