Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

Hargrove, Tatiana Y.; Friggeri, Laura; Wawrzak, Zdzislaw; Qi, Aidong; Hoekstra, William J.; Schotzinger, Robert J.; York, John D.; Guengerich, F. Peter; Lepesheva, Galina I.

doi:10.1074/jbc.m117.778308

Cited by 459Antifungal resistance and susceptibilityFungal Plant Pathogen ControlMicrobial Natural Products and Biosynthesis

Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

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Hargrove, Tatiana Y., Friggeri, Laura, Wawrzak, Zdzislaw, Qi, Aidong, Hoekstra, William J., Schotzinger, Robert J., York, John D., Guengerich, F. Peter +1 more·2017·Journal of Biological Chemistry

DOI 10.1074/jbc.m117.778308PMC PMC5399120

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Abstract

With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression), the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and is the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure. We report the catalytic properties, ligand-binding profiles, and inhibition of enzymatic activity of C. albicans CYP51 by clinical antifungal drugs that are used systemically (fluconazole, voriconazole, ketoconazole, itraconazole, and posaconazole) and topically (miconazole and clotrimazole) and by a tetrazole-based drug candidate, VT-1161 (oteseconazole: ( R )-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1 H -tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol). Among the compounds tested, the first-line drug fluconazole was the weakest inhibitor, whereas posaconazole and VT-1161 were the strongest CYP51 inhibitors. We determined the X-ray structures of C. albicans CYP51 complexes with posaconazole and VT-1161, providing a molecular mechanism for the potencies of these drugs, including the activity of VT-1161 against Candida krusei and Candida glabrata , pathogens that are intrinsically resistant to fluconazole. Our comparative structural analysis outlines phylum-specific CYP51 features that could direct future rational development of more efficient broad-spectrum antifungals.

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Structural analysis of C. albicans Erg11 demonstrated that some substitutions involve residues exposed in the active-site cavity and directly affect azole binding, while others occur on the proximal surface and may indirectly contribute to azole resistance.
“Structural analysis of C. albicans Erg11 demonstrated that while some substitutions involve residues that are exposed in the active-site cavity (directly affecting azole binding), others occur on the proximal surface of the enzyme and may indirectly contribute to azole resistance (for example, by influencing interactions with cytochrome P450 reductase)11.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [11]
The crystal structure of C. albicans Erg11 has been resolved.
“the crystal structure of the Erg11 protein of C. albicans has been resolved”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [139]
Other Erg11 substitutions not predicted to directly interact with azole binding, such as G450E on the fungal CYP51-specific β5-hairpin, may indirectly affect resistance through interaction with cytochrome P450 reductase-Erg11 interactions.
“other substitutions that are not predicted to directly interact with azole binding, such as the G450E substitution found on the fungal CYP51-specific β5-hairpin, may indirectly affect resistance through interaction with cytochrome P450 reductase–Erg11 interactions.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [139]
Some Erg11 substitutions (Y132F/H, K143R, G307S, S405F) are located on the exposed active-site cavity of Erg11 and presumably directly influence or interfere with azole binding.
“some substitutions, such as Y132F/H, K143R, G307S and S405F, are located on the exposed active-site cavity of the Erg11 protein and presumably directly influence or interfere with azole binding”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [139]

UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
Hidden Killers: Human Fungal Infections
Brown, G. D., Denning, D. W., Gow, N. A. R., Levitz, S. M., Netea, M. G., & White, T. C. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004404 · Cited by 4,284 · see citing works
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America
Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., Reboli, A. C., Schuster, M. G., Vazquez, J. A., Walsh, T. J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ933 · Cited by 4,200 · see citing works
Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions
Krissinel, E., & Henrick, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904026460 · Cited by 3,785 · see citing works
Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America
Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191 · see citing works
Cytochrome P-450: Structure, Mechanism, and Biochemistry
de Montellano, O., & Paul, R. (1986) · Medical Entomology and Zoology · Cited by 2,667 · see citing works
Cytochrome P450: Structure, mechanism, and biochemistry
PRYOR, W. A. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)83807-x · Cited by 1,610 · see citing works
Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance
White, T. C., Marr, K. A., & Bowden, R. A. (1998) · Clinical Microbiology Reviews · doi:10.1128/cmr.11.2.382 · Cited by 1,353 · see citing works
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution
Schlichting, I., Berendzen, J., Chu, K., Stock, A., Maves, S. A., Benson, D. E., Sweet, R. M., Ringe, D., Petsko, G. A., & Sligar, S. G. (2000) · Science · doi:10.1126/science.287.5458.1615 · Cited by 1,333 · see citing works
Invasive candidiasis
Kullberg, B. J., & Arendrup, M. C. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1315399 · Cited by 1,315 · see citing works
A graphical user interface to the CCP 4 program suite
Potterton, E. A., Briggs, P., Turkenburg, M., & Dodson, E. J. (2003) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444903008126 · Cited by 1,216 · see citing works
Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences.
Gotoh, O. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48462-1 · Cited by 1,210 · see citing works
Molecular Evidence for the Early Colonization of Land by Fungi and Plants
Heckman, D. S., Geiser, D. M., Eidell, B. R., Stauffer, R. L., Kardos, N. L., & Hedges, S. B. (2001) · Science · doi:10.1126/science.1061457 · Cited by 1,020 · see citing works
The Early Evolution of Eukaryotes: A Geological Perspective
Knoll, A. H. (1992) · Science · doi:10.1126/science.1585174 · Cited by 684 · see citing works
Epidemiology and risk factors for invasive candidiasis
Yapar, N. (2014) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s40160 · Cited by 610 · see citing works
Candida albicans cell-type switching and functional plasticity in the mammalian host
Noble, S. M., Gianetti, B. A., & Witchley, J. N. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.157 · Cited by 518 · see citing works
Sterol 14α-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms
Lepesheva, G. I., & Waterman, M. R. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.07.018 · Cited by 476 · see citing works
Self-citation
Azole antifungal agents: Emphasis on new triazoles
Saag, M. S., & Dismukes, W. E. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.1.1 · Cited by 474 · see citing works
How to bolster the antifungal pipeline
Denning, D., & Bromley, M. (2015) · Science · doi:10.1126/science.aaa6097 · Cited by 462 · see citing works
Molecular basis of resistance to azole antifungals.
Lupetti, A. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02280-3 · Cited by 449 · see citing works
Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans
Marichal, P., Koymans, L., Willemsens, S., Bellens, D., Verhasselt, P., Luyten, W., Borgers, M., Ramaekers, F. C. S., Odds, F. C., & Vanden Bossche, H. (1999) · Microbiology · doi:10.1099/00221287-145-10-2701 · Cited by 382 · see citing works
Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen
Ene, I. V., Adya, A. K., Wehmeier, S., Brand, A. C., MacCallum, D. M., Gow, N. A. R., & Brown, A. J. P. (2012) · Cellular Microbiology · doi:10.1111/j.1462-5822.2012.01813.x · Cited by 313 · see citing works
Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature
Morio, F., Loge, C., Besse, B., Hennequin, C., & Le Pape, P. (2010) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2009.11.006 · Cited by 279 · see citing works
Triazole Antifungal Agents in Invasive Fungal Infections
Lass‐Flörl, C. (2011) · Drugs · doi:10.2165/11596540-000000000-00000 · Cited by 272 · see citing works
Candidemia and invasive candidiasis in adults: A narrative review
Antinori, S., Milazzo, L., Sollima, S., Galli, M., & Corbellino, M. (2016) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2016.06.029 · Cited by 259 · see citing works
Inhibition of Cytochromes P450 by Antifungal Imidazole Derivatives
Zhang, W., Ramamoorthy, Y., Kilicarslan, T., Nolte, H., Tyndale, R. F., & Sellers, E. M. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.3.314 · Cited by 252 · see citing works
Design and optimization of highly-selective fungal CYP51 inhibitors
Hoekstra, W. J., Garvey, E. P., Moore, W. R., Rafferty, S. W., Yates, C. M., & Schotzinger, R. J. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.05.068 · Cited by 195 · see citing works
Self-citation
Cell biology of Candida albicans–host interactions
Dantas, A. D. S., Lee, K. K., Raziunaite, I., Schaefer, K., Wagener, J., Yadav, B., & Gow, N. A. R. (2016) · Current Opinion in Microbiology · doi:10.1016/j.mib.2016.08.006 · Cited by 170 · see citing works
Structure-Functional Characterization of Cytochrome P450 Sterol 14α-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs
Hargrove, T. Y., Wawrzak, Z., Lamb, D. C., Guengerich, F. P., & Lepesheva, G. I. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677310 · Cited by 166 · see citing works
Self-citation
Structural basis for conservation in the CYP51 family
Lepesheva, G. I., & Waterman, M. R. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.06.006 · Cited by 147 · see citing works
Self-citation
Structural Insights into Inhibition of Sterol 14α-Demethylase in the Human Pathogen Trypanosoma cruzi
Lepesheva, G. I., Hargrove, T. Y., Anderson, S. M., Kleshchenko, Y. Y., Furtak, V. A., Wawrzak, Z., Villalta, F., & Waterman, M. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.133215 · Cited by 146 · see citing works
Self-citation
Sterol 14α-Demethylase as a Potential Target for Antitrypanosomal Therapy: Enzyme Inhibition and Parasite Cell Growth
Lepesheva, G. I., Ott, R. D., Hargrove, T. Y., Kleshchenko, Y. Y., Schuster, I., Nes, W. D., Hill, G. C., Villalta, F., & Waterman, M. R. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.10.011 · Cited by 138 · see citing works
Self-citation
Substrate Preferences and Catalytic Parameters Determined by Structural Characteristics of Sterol 14α-Demethylase (CYP51) from Leishmania infantum
Hargrove, T. Y., Wawrzak, Z., Liu, J., Nes, W. D., Waterman, M. R., & Lepesheva, G. I. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.237099 · Cited by 125 · see citing works
Self-citation
CYP51 from Trypanosoma cruzi
Lepesheva, G. I., Zaitseva, N. G., Nes, W. D., Zhou, W., Arase, M., Liu, J., Hill, G. C., & Waterman, M. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510317200 · Cited by 120 · see citing works
Self-citation
The development of fluconazole resistance in Candida albicans – an example of microevolution of a fungal pathogen
Morschhäuser, J. (2016) · Journal of Microbiology · doi:10.1007/s12275-016-5628-4 · Cited by 118 · see citing works
Crystal Structures of Trypanosoma brucei Sterol 14α-Demethylase and Implications for Selective Treatment of Human Infections
Lepesheva, G. I., Park, H.-W., Hargrove, T. Y., Vanhollebeke, B., Wawrzak, Z., Harp, J. M., Sundaramoorthy, M., Nes, W. D., Pays, É., Chaudhuri, M., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.067470 · Cited by 116 · see citing works
Self-citation
Candida albicans Biofilm Development and Its Genetic Control
Desai, J. V., & Mitchell, A. P. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mb-0005-2014 · Cited by 94 · see citing works
Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis
Garvey, E. P., HOEKSTRA, W., Schotzinger, R. J., Sobel, J. D., Lilly, E. A., & Fidel, P. L. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00185-15 · Cited by 83 · see citing works
Self-citation
CYP51 from Trypanosoma brucei Is Obtusifoliol-Specific
Lepesheva, G. I., Nes, W. D., Zhou, W., Hill, G. C., & Waterman, M. R. (2004) · Biochemistry · doi:10.1021/bi048967t · Cited by 79 · see citing works
Self-citation
Complexes of Trypanosoma cruzi Sterol 14α-Demethylase (CYP51) with Two Pyridine-based Drug Candidates for Chagas Disease
Hargrove, T. Y., Wawrzak, Z., Alexander, P. W., Chaplin, J. H., Keenan, M., Charman, S. A., Perez, C. J., Waterman, M. R., Chatelain, E., & Lepesheva, G. I. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.497990 · Cited by 79 · see citing works
Self-citation
Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong In Vitro Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds
Schell, W. A., Jones, A. M., Garvey, E. P., Hoekstra, W. J., Schotzinger, R. J., & Alexander, B. D. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01817-16 · Cited by 74 · see citing works
Self-citation
Role of isavuconazole in the treatment of invasive fungal infections
Wilson, D. T., DiMondi, V. P., Johnson, S., Jones, T. M., & Drew, R. H. (2016) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s90335 · Cited by 72 · see citing works
Structural complex of sterol 14α-demethylase (CYP51) with 14α-methylenecyclopropyl-Δ7-24, 25-dihydrolanosterol
Hargrove, T. Y., Wawrzak, Z., Liu, J., Waterman, M. R., Nes, W. D., & Lepesheva, G. I. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m021865 · Cited by 67 · see citing works
Self-citation
VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis
Lepesheva, G. I., Hargrove, T. Y., Rachakonda, G., Wawrzak, Z., Pomel, S., Cojean, S., Nde, P. N., Nes, W. D., Locuson, C. W., Calcutt, M. W., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv228 · Cited by 66 · see citing works
Self-citation
Antitrypanosomal Lead Discovery: Identification of a Ligand-Efficient Inhibitor of Trypanosoma cruzi CYP51 and Parasite Growth
Andriani, G., Amata, E., Beatty, J. W., Clements, Z. T., Coffey, B. J., Courtemanche, G., Devine, W. G., Erath, J., Juda, C. E., Wawrzak, Z., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400012e · Cited by 65 · see citing works
Self-citation
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Hargrove, T. Y., Friggeri, L., Wawrzak, Z., Sivakumaran, S., Yazlovitskaya, E. M., Hiebert, S. W., Guengerich, F. P., Waterman, M. R., & Lepesheva, G. I. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m069229 · Cited by 61 · see citing works
Self-citation
Sterol biosynthesis inhibitors
(1989) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(89)90024-3 · Cited by 61 · see citing works
Structural Basis for Rational Design of Inhibitors Targeting Trypanosoma cruzi Sterol 14α-Demethylase: Two Regions of the Enzyme Molecule Potentiate Its Inhibition
Friggeri, L., Hargrove, T. Y., Rachakonda, G., Williams, A. D., Wawrzak, Z., Santo, R. D., Vita, D. D., Waterman, M. R., Tortorella, S., Villalta, F., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500739f · Cited by 45 · see citing works
Self-citation
Folding Requirements Are Different between Sterol 14α-Demethylase (CYP51) from Mycobacterium tuberculosis and Human or Fungal Orthologs
Lepesheva, G. I., Podust, L. M., Bellamine, A., & Waterman, M. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102767200 · Cited by 45 · see citing works
Self-citation
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Mane, A. K., Vidhate, P., Kusro, C., Waman, V., Saxena, V., Kulkarni‐Kale, U., & Risbud, A. (2015) · Mycoses · doi:10.1111/myc.12439 · Cited by 41 · see citing works
Clinical Candidate VT-1161's Antiparasitic EffectIn Vitro, Activity in a Murine Model of Chagas Disease, and Structural Characterization in Complex with the Target Enzyme CYP51 from Trypanosoma cruzi
Hoekstra, W. J., Hargrove, T. Y., Wawrzak, Z., Batista, D. D. G. J., da Silva, C. F., Nefertiti, A. S. G., Rachakonda, G., Schotzinger, R. J., Villalta, F., Soeiro, M. D. N. C., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02287-15 · Cited by 37 · see citing works
Self-citation
Effect of imidazole antifungals on the development of germ tubes by strains of Candida albicans
Johnson, E. M., Richardson, M. D., & Warnock, D. W. (1983) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/12.4.303 · Cited by 32 · see citing works
Conformational dynamics and molecular interaction reactions of recombinant cytochrome P450scc (CYP11A1) detected by fluorescence energy transfer
Lepesheva, G. I., Strushkevich, N. V., & Usanov, S. A. (1999) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(99)00156-9 · Cited by 30 · see citing works
Self-citation
How can We Bolster the Antifungal Drug Discovery Pipeline?
Jampílek, J. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0124 · Cited by 30 · see citing works
Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition
Cherkesova, T. S., Hargrove, T. Y., Vanrell, M. C., Ges, I. A., Usanov, S. A., Romano, P. S., & Lepesheva, G. I. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.08.030 · Cited by 21 · see citing works
Self-citation
Safety, clinical effectiveness and trough plasma concentrations of intravenous posaconazole in patients with haematological malignancies and/or undergoing allogeneic haematopoietic stem cell transplantation: off-trial experience
Jeong, W., Haywood, P., Shanmuganathan, N., Lindsay, J., Urbancic, K. F., Ananda-Rajah, M. R., Chen, W., Bajel, A. R., Ritchie, D., Grigg, A., et al. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkw322 · Cited by 20 · see citing works

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Zhang, J., Li, L., Lv, Q., Yan, L., Wang, Y., & Jiang, Y. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00691 · Cited by 249 · see citing works
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Osset-Trénor, P., Pascual‐Ahuir, A., & Proft, M. (2023) · Journal of Fungi · doi:10.3390/jof9050565 · Cited by 103 · see citing works
Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans
Nishimoto, A. T., Sharma, C., & Rogers, P. D. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz400 · Cited by 102 · see citing works
Spectroscopic characterization (IR, UV-Vis), and HOMO-LUMO, MEP, NLO, NBO Analysis and the Antifungal Activity for 4-Bromo-N-(2-nitrophenyl) benzamide; Using DFT Modeling and In silico Molecular Docking
Alghamdi, S. K., Abbas, F., Hussein, R. K., Alhamzani, A. G., & El-Shamy, N. T. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134001 · Cited by 102 · see citing works
Discovery of Novel Fungal Lanosterol 14α-Demethylase (CYP51)/Histone Deacetylase Dual Inhibitors to Treat Azole-Resistant Candidiasis
Han, G., Liu, N., Li, C., Tu, J., Li, Z., & Sheng, C. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00102 · Cited by 85 · see citing works
Candida albicanstargets that potentially synergize with fluconazole
Lu, H., Shrivastava, M., Whiteway, M., & Jiang, Y. (2021) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1884641 · Cited by 81 · see citing works
Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds
Karaburun, A. Ç., Kaya, B., Çevik, U. A., Osmani̇ye, D., Sağlık, B. N., Levent, S., Özkay, Y., Atlı, Ö., Koparal, A. S., & Kaplancıklı, Z. A. (2019) · Molecules · doi:10.3390/molecules24010191 · Cited by 80 · see citing works
Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles
Elias, R., Benhamou, R. I., Jaber, Q. Z., Dorot, O., Zada, S. L., Oved, K., Pichinuk, E., & Fridman, M. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.07.003 · Cited by 75 · see citing works
Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect
Bassyouni, F. A., Tarek, M., Salama, A., Ibrahim, B. M. M., Dine, S. S. E., Yassin, N., el Din, A. A. G., Moharam, M. E., & Abdel‐Rehim, M. (2021) · Molecules · doi:10.3390/molecules26082370 · Cited by 75 · see citing works
Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity
Hargrove, T. Y., Garvey, E. P., Hoekstra, W. J., Yates, C. M., Wawrzak, Z., Rachakonda, G., Villalta, F., & Lepesheva, G. I. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00570-17 · Cited by 75 · see citing works
Self-citation
Synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents
Nalawade, J., Shinde, A. D., Chavan, A., Patil, S. P., Suryawanshi, M., Modak, M. A., Choudhari, P. B., Bobade, V. D., & Mhaske, P. C. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.06.074 · Cited by 74 · see citing works
Advances in preclinical approaches to Chagas disease drug discovery
Villalta, F., & Rachakonda, G. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1652593 · Cited by 72 · see citing works
A Structural View on Medicinal Chemistry Strategies against Drug Resistance
Agnello, S., Brand, M., Chellat, M. F., Gazzola, S., & Riedl, R. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201802416 · Cited by 70 · see citing works
Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde
Alves, D. D. N., Monteiro, A., Andrade, P. N., Lazarini, J. G., Abílio, G. M. F., Guerra, F. Q. S., Scotti, M. T., Scotti, L., Rosalen, P. L., & de Castro, R. D. (2020) · Molecules · doi:10.3390/molecules25245969 · Cited by 68 · see citing works
Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives
Branda, F., Petrosillo, N., Ceccarelli, G., Giovanetti, M., VITO, A. D., Madeddu, G., Scarpa, F., & Ciccozzi, M. (2025) · Infectious Disease Reports · doi:10.3390/idr17040091 · Cited by 68 · see citing works
Understanding the mechanisms of resistance to azole antifungals in Candida species
Li, Y., Hind, C. K., Furner-Pardoe, J., Sutton, J. M., & Rahman, K. M. (2025) · JAC-Antimicrobial Resistance · doi:10.1093/jacamr/dlaf106 · Cited by 66 · see citing works
In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens
Qureshi, K. A., Imtiaz, M., Parvez, A., Rai, P. K., Jaremko, M., Emwas, A.-H. M., Bholay, A. D., & Fatmi, M. Q. (2022) · Antibiotics · doi:10.3390/antibiotics11010079 · Cited by 63 · see citing works
Synthesis and adsorption properties investigation of Fe3O4@ZnAl-LDH@MIL-53(Al) for azole fungicides removal from environmental water
Lu, Z.-H., Senosy, I. A., Zhou, D., Yang, Z., Guo, H., & Liu, X. (2021) · Separation and Purification Technology · doi:10.1016/j.seppur.2021.119282 · Cited by 61 · see citing works
CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM)
Debnath, A., Calvet, C. M., Jennings, G. K., Zhou, W., Aksenov, A. A., Luth, M. R., Abagyan, R. A., Nes, W. D., McKerrow, J. H., & Podust, L. M. (2017) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0006104 · Cited by 61 · see citing works
The Evolution of Azole Resistance in Candida albicans Sterol 14α-Demethylase (CYP51) through Incremental Amino Acid Substitutions
Warrilow, A. G., Nishimoto, A. T., Parker, J. E., Price, C. L., Flowers, S. A., Kelly, D. E., Rogers, P. D., & Kelly, S. L. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02586-18 · Cited by 60 · see citing works
Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Potent Antifungal Agents
Karaburun, A. Ç., Çevik, U. A., Osmani̇ye, D., Sağlık, B. N., Çavuşoğlu, B. K., Levent, S., Özkay, Y., Koparal, A. S., Behçet, M., & Kaplancıklı, Z. A. (2018) · Molecules · doi:10.3390/molecules23123129 · Cited by 60 · see citing works
Magnetic MXene based metal organic frameworks composites: Synthesis, characterization and application
Lu, Z.-H., Tian, Q., Zhou, D., Chen, M., Cao, Y., Zhuang, L.-Y., Liu, X., Yang, Z., & Senosy, I. A. (2022) · Journal of environmental chemical engineering · doi:10.1016/j.jece.2022.108037 · Cited by 56 · see citing works
New indazole–1,2,3–triazoles as potent antimicrobial agents: Design, synthesis, molecular modeling and in silico ADME profiles
Gandham, S. K., Kudale, A. A., Allaka, T. R., Chepuri, K., & Jha, A. (2023) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2023.136714 · Cited by 56 · see citing works
Design, synthesis, and structure-activity relationship studies of novel tetrazole antifungal agents with potent activity, broad antifungal spectrum and high selectivity
Qian, A., Zheng, Y., Wang, R., Wei, J., Cui, Y., Cao, X., & Yang, Y. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.12.040 · Cited by 55 · see citing works
Human cytochrome P450 enzymes 5–51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition – toxic effects and benefits
Rendić, S., & Guengerich, F. P. (2018) · Drug Metabolism Reviews · doi:10.1080/03602532.2018.1483401 · Cited by 54 · see citing works
Self-citation
Review on Structures of Pesticide Targets
Li, X., Yang, X., Zheng, X., Bai, M., & Hu, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197144 · Cited by 54 · see citing works
Immobilized fungal enzymes: Innovations and potential applications in biodegradation and biosynthesis
Gao, Y., Shah, K., Kwok, I. Y., Wang, M., Rome, L. H., & Mahendra, S. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.107936 · Cited by 54 · see citing works
In Vitro Activities of the Novel Investigational Tetrazoles VT-1161 and VT-1598 Compared to the Triazole Antifungals against Azole-Resistant Strains and Clinical Isolates of Candida albicans
Nishimoto, A. T., Wiederhold, N. P., Flowers, S. A., Zhang, Q., Kelly, S. L., Morschhäuser, J., Yates, C. M., Hoekstra, W. J., Schotzinger, R. J., Garvey, E. P., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00341-19 · Cited by 52 · see citing works
Self-citation
Isolation and Characterization of an Endophytic Fungus Colletotrichum coccodes Producing Tyrosol From Houttuynia cordata Thunb. Using ITS2 RNA Secondary Structure and Molecular Docking Study
Talukdar, R., Padhi, S., Rai, A. K., Masi, M., Evidente, A., Jha, D. K., Cimmino, A., & Tayung, K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.650247 · Cited by 52 · see citing works
Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost
Bédard, C., Gagnon‐Arsenault, I., Boisvert, J., Plante, S., Dubé, A. K., Pageau, A., Fijarczyk, A., Sharma, J., Maroc, L., Shapiro, R. S., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01819-2 · Cited by 50 · see citing works
Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 2^3 Full Factorial Design
Alyahya, E. M., Alwabsi, K., Aljohani, A. E., Albalawi, R., El‐Sherbiny, M., Ahmed, R., Mortagi, Y. I., & Qushawy, M. K. E. (2023) · Polymers · doi:10.3390/polym15040995 · Cited by 49 · see citing works
Sterol 14α-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
Friggeri, L., Hargrove, T. Y., Wawrzak, Z., Blobaum, A. L., Rachakonda, G., Lindsley, C. W., Villalta, F., Nes, W. D., Botta, M., Guengerich, F. P., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00641 · Cited by 48 · see citing works
Self-citation
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Zhao, L., Tian, L., Sun, N., Sun, Y., Chen, Y., Wang, X., Zhao, S., Su, X., Zhao, D., & Cheng, M. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.047 · Cited by 48 · see citing works
Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents
Çevik, U. A., Çeli̇k, İ., Işık, A., Pillai, R. R., Tallei, T. E., Yadav, R., Özkay, Y., & Kaplancıklı, Z. A. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.132095 · Cited by 48 · see citing works
Thiophene-Derived Schiff Base Complexes: Synthesis, Characterization, Antimicrobial Properties, and Molecular Docking
Nayab, S., Alam, A., Ahmad, N., Khan, S. W., Khan, W., Shams, D. F., Shah, M. I. A., Ateeq, M. F., Shah, S. K., & Lee, H. (2023) · ACS Omega · doi:10.1021/acsomega.2c08266 · Cited by 47 · see citing works
Effects of Acetone Fraction From Buchenavia tomentosa Aqueous Extract and Gallic Acid on Candida albicans Biofilms and Virulence Factors
Teodoro, G. R., Gontijo, A. V. L., Salvador, M. J., Tanaka, M. H., Brighenti, F. L., Delbem, A. C. B., Delbem, Á. C. B., & Koga‐Ito, C. Y. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00647 · Cited by 47 · see citing works
Antimicrobial activity and molecular docking screening of bioactive components of Antirrhinum majus (snapdragon) aerial parts
Saqallah, F. G., Hamed, W. M. A. A. S., Talib, W. H., Dianita, R., & Wahab, H. A. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e10391 · Cited by 46 · see citing works
Strategies of targeting CYP51 for IFIs therapy: Emerging prospects, opportunities and challenges
Zhang, R., Wang, Y., Wu, A., Wang, J., & Zhang, J. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115658 · Cited by 46 · see citing works
Azole Resistance Reduces Susceptibility to the Tetrazole Antifungal VT-1161
Monk, B. C., Keniya, M. V., Sabherwal, M., Wilson, R. K., Graham, D. O., Hassan, H. F., Chen, D., & Tyndall, J. D. A. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02114-18 · Cited by 46 · see citing works
Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future
Guengerich, F. P. (2022) · Advances in pharmacology · doi:10.1016/bs.apha.2021.12.001 · Cited by 45 · see citing works
Self-citation
Indole clubbed 2,4‐thiazolidinedione linked 1,2,3‐triazole as a potent antimalarial and antibacterial agent against drug‐resistant strain and molecular modeling studies
Upadhyay, D. B., Mokariya, J. A., Patel, P. J., Patel, S. G., Das, A., Nandi, A., Nogales, J., More, N., Kumar, A., Rajani, D. P., et al. (2024) · Archiv der Pharmazie · doi:10.1002/ardp.202300673 · Cited by 45 · see citing works
Design, synthesis, and structure-activity relationship studies of novel triazole agents with strong antifungal activity against Aspergillus fumigatus
Ding, Z., Ni, T., Xie, F., Hao, Y., Yu, S., Chai, X., Jin, Y., Wang, T., Jiang, Y., & Zhang, D. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2020.126951 · Cited by 44 · see citing works
Molecular docking studies and biological evaluation of isoxazole-carboxamide derivatives as COX inhibitors and antimicrobial agents
Hawash, M., Jaradat, N. A., Abualhasan, M., Qaoud, M. T., Joudeh, Y., Jaber, Z., Sawalmeh, M., Zarour, A., Mousa, A., & Arar, M. (2022) · 3 Biotech · doi:10.1007/s13205-022-03408-8 · Cited by 42 · see citing works
Synthesis, Molecular Docking Studies, In Vitro Antimicrobial and Antifungal Activities of Novel Dipeptide Derivatives Based on N-(2-(2-Hydrazinyl-2-oxoethylamino)-2-oxoethyl)-Nicotinamide
Moustafa, G. O., Khalaf, H. S., Naglah, A. M., Al‐Wasidi, A. S., Al-Jafshar, N. M., & Awad, H. M. (2018) · Molecules · doi:10.3390/molecules23040761 · Cited by 41 · see citing works
Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases
Lamb, D. C., Hargrove, T. Y., Zhao, B., Wawrzak, Z., Goldstone, J. V., Nes, W. D., Kelly, S. L., Waterman, M. R., Stegeman, J. J., & Lepesheva, G. I. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa260 · Cited by 40 · see citing works
Self-citation
Design, synthesis, and antimicrobial activity of novel coumarin derivatives: An in-silico and in-vitro study
Nuha, D., Evren, A. E., Kapusiz, Ö., Gül, Ü. D., Gündoğdu-Karaburun, N., Karaburun, A. Ç., & Berber, H. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134166 · Cited by 39 · see citing works
Molecular Dynamics Investigations of Binding Mechanism for Triazoles Inhibitors to CYP51
Shi, N., Zheng, Q., & Zhang, H. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.586540 · Cited by 39 · see citing works
Antibacterial, Antifungal, and Antioxidant Activities of Silver Nanoparticles Biosynthesized from Bauhinia tomentosa Linn
Senthil, R., Subramaniyan, S., Karunanithi, N., Vasanthakumar, P., Kutzner, A., Kim, P., & Heese, K. (2021) · Antioxidants · doi:10.3390/antiox10121959 · Cited by 38 · see citing works
Anti-Candida albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART
da Silva, A. F., Farias, J. R., Franco, D. C. G., Galiza, A. A., Motta, E. P., Oliveira, A. D. S., Vasconcelos, C. C., Cartágenes, M. D. S. D. S., da Rocha, C. Q., Silva, M. C. P. D., et al. (2022) · Metabolites · doi:10.3390/metabo12111014 · Cited by 37 · see citing works
Developing Novel Coumarin-Containing Azoles Antifungal Agents by the Scaffold Merging Strategy for Treating Azole-Resistant Candidiasis
Yan, Z.-Z., Huang, Y., Zhao, D., Li, Z., Wang, X., Guo, M., Wei, Y., Wang, Y., Mou, Y., Hou, Z., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01254 · Cited by 37 · see citing works
Synthesis, single crystal, TD-DFT, molecular dynamics simulation and DNA binding studies of carbothioamide analog
Rana, M., Ahmedi, S., Fatima, A., Ahmad, S., Nouman, Siddiqui, N., Raza, K., Manzoor, N., Javed, S., & Rahisuddin, R. (2023) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2023.135701 · Cited by 37 · see citing works
Distorted Gold(I)–Phosphine Complexes as Antifungal Agents
Dennis, E. K., Kim, J. H., Parkin, S., Awuah, S. G., & Garneau‐Tsodikova, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01436 · Cited by 36 · see citing works
Investigation of Novel Quinoline–Thiazole Derivatives as Antimicrobial Agents: In Vitro and In Silico Approaches
Evren, A. E., Karaduman, A. B., Sağlık, B. N., Özkay, Y., & Yurttaş, L. (2022) · ACS Omega · doi:10.1021/acsomega.2c06871 · Cited by 35 · see citing works
Design, synthesis, and evaluation of novel tetrazoles featuring isoxazole moiety as highly selective antifungal agents
Ni, T., Chi, X., Xie, F., Li, L., Wu, H., Hao, Y., Wang, X., Zhang, D., & Jiang, Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.115007 · Cited by 35 · see citing works
Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole–Thiadiazole Hybrids
Çeli̇k, İ., Çevik, U. A., Karayel, A., Işık, A., Kayış, U., Gül, Ü. D., Bostancı, H. E., KONCA, S. F., Özkay, Y., & Kaplancıklı, Z. A. (2022) · ACS Omega · doi:10.1021/acsomega.2c06142 · Cited by 35 · see citing works
Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51
Zhao, S., Peng, W. J., Wu, M., Zhang, X., Zhao, L., Jiang, X., Hao, C., Su, X., Zhao, D., & Cheng, M. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.04.054 · Cited by 34 · see citing works
Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure
Suchodolski, J., Derkacz, D., Muraszko, J., Panek, J. J., Jezierska, A., Łukaszewicz, M., & Krasowska, A. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12040314 · Cited by 34 · see citing works
Strategies to Better Target Fungal Squalene Monooxygenase
Sagatova, A. A. (2021) · Journal of Fungi · doi:10.3390/jof7010049 · Cited by 34 · see citing works
Investigation of Novel Mucorales Fungal Inhibitors: Synthesis, In‐Silico Study and Anti‐Fungal Potency of Novel Class of Coumarin‐6‐Sulfonamides‐Thiazole and Thiadiazole Hybrids
Sabt, A., Abdelrahman, M. T., Abdelraof, M., & Rashdan, H. R. M. (2022) · ChemistrySelect · doi:10.1002/slct.202200691 · Cited by 33 · see citing works
Construction of antifungal dual-target (SE, CYP51) pharmacophore models and the discovery of novel antifungal inhibitors
Dong, Y., Liu, M., Wang, J., Ding, Z., & Sun, B. (2019) · RSC Advances · doi:10.1039/c9ra03713f · Cited by 32 · see citing works
Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action
da Silva, C. R., Sá, L. G. D. A. V., dos Santos, E. V., Ferreira, T. L., Coutinho, T. D. N. P., Moreira, L. E. A., Campos, R. D. S., de Andrade, C. R., da Silva, W. M. B., Carneiro, I. D. S., et al. (2022) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001526 · Cited by 32 · see citing works
Transcriptomics analysis of propiconazole-treated Cochliobolus sativus reveals new putative azole targets in the plant pathogen
Somani, D., Adhav, R., Prashant, R., & Kadoo, N. Y. (2019) · Functional & Integrative Genomics · doi:10.1007/s10142-019-00660-9 · Cited by 31 · see citing works
Enhanced removal efficiency towards azole fungicides from environmental water using a metal organic framework functionalized magnetic lignosulfonate
Lu, Z.-H., Lv, D., Zhou, D., Yang, Z., Wang, M., Senosy, I. A., Liu, X., Chen, M., & Zhuang, L.-Y. (2021) · Separation and Purification Technology · doi:10.1016/j.seppur.2021.119785 · Cited by 31 · see citing works
K143R Amino Acid Substitution in 14-α-Demethylase (Erg11p) Changes Plasma Membrane and Cell Wall Structure of Candida albicans
Derkacz, D., Bernat, P., & Krasowska, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031631 · Cited by 31 · see citing works
Impact of Homologous Resistance Mutations from Pathogenic Yeast on Saccharomyces cerevisiae Lanosterol 14α-Demethylase
Sagatova, A. A., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02242-17 · Cited by 31 · see citing works
Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide
Khalaf, H. S., Naglah, A. M., Al-Omar, M. A., Moustafa, G. O., Awad, H. M., & Bakheit, A. H. H. (2020) · Molecules · doi:10.3390/molecules25163589 · Cited by 30 · see citing works
Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases
Monk, B. C., & Keniya, M. V. (2021) · Journal of Fungi · doi:10.3390/jof7020067 · Cited by 30 · see citing works
Multi-site fungicides suppress banana Panama disease, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4
Cannon, S. J., Kay, W. T., Kilaru, S., Schuster, M., Gurr, S. J., & Steinberg, G. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010860 · Cited by 30 · see citing works
Cytochrome P450 monooxygenase systems: Diversity and plasticity for adaptive stress response
Mokhosoev, I. M., Astakhov, D. V., Terentiev, A. A., & Moldogazieva, N. T. (2024) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2024.09.003 · Cited by 29 · see citing works
New azole antifungals with a fused triazinone scaffold
Montoir, D., Guillon, R., Gazzola, S., Ourliac‐Garnier, I., Soklou, K. E., Tonnerre, A., Picot, C., Planchat, A., Pagniez, F., Pape, P. L., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112082 · Cited by 29 · see citing works
Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans
Binjubair, F. A., Parker, J. E., Warrilow, A. G. S., Puri, K., Braidley, P. J., Tatar, E., Kelly, S. L., Kelly, D. E., & Simons, C. (2020) · ChemMedChem · doi:10.1002/cmdc.202000250 · Cited by 29 · see citing works
Novel naphthylamide derivatives as dual-target antifungal inhibitors: Design, synthesis and biological evaluation
An, Y., Dong, Y., Liu, M., Han, J., Zhao, L., & Sun, B. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112991 · Cited by 29 · see citing works
Design, synthesis and bioactivity evaluation of novel arylalkene-amide derivatives as dual-target antifungal inhibitors
Sun, B., Dong, Y., An, Y., Liu, M., Han, J., Zhao, L., & Liu, X. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112645 · Cited by 29 · see citing works
Synthesis, characterization, biological activities, and computational studies of pyrazolyl–thiazole derivatives of thiophene
Bhagwat, S. K., Pawar, T. J., Kulkarni, S. A., Patil, A. A., More, R. A., Jiménez‐Halla, J. Ó. C., Alvarado-Salazar, J. A., Olivares-Romero, J. L., Muteeb, G., Delgado‐Alvarado, E., et al. (2024) · RSC Advances · doi:10.1039/d4ra06228k · Cited by 28 · see citing works
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Shafiei, M., Toreyhi, H., Firoozpour, L., Akbarzadeh, T., Amini, M., Hosseinzadeh, E., Hashemzadeh, M., Peyton, L., Lotfali, E., & Foroumadi, A. (2021) · ACS Omega · doi:10.1021/acsomega.1c04016 · Cited by 28 · see citing works
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Abdelgawad, M. A., Hamed, A. A., Nayl, A. A., Badawy, M. S. E. M., Ghoneim, M. M., Sayed, A. M., Hassan, H. M., & Gamaleldin, N. M. (2022) · Molecules · doi:10.3390/molecules27051704 · Cited by 28 · see citing works
Design, synthesis and biological evaluation of isatin-benzotriazole hybrids as new class of anti-Candida agents
Singh, A., Kaur, K., Kaur, H., Mohana, P., Arora, S., Bedi, N., Chadha, R., & Bedi, P. M. S. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134456 · Cited by 28 · see citing works
Hirshfeld Surface analysis, spectroscopic, biological studies and molecular docking of (4E)-4-((naphthalen-2-yl)methyleneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one
Eltayeb, N. E., Şen, F., Lasri, J., Hussien, M. A., Elsilk, S. E., Babgi, B. A., Gökçe, H., & Sert, Y. (2019) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2019.127315 · Cited by 27 · see citing works
Design, synthesis, antimicrobial evaluation and in silico studies of symmetrical bis (urea-1,2,3-triazole) hybrids
Poonia, N., Lal, K., & Kumar, A. (2020) · Research on Chemical Intermediates · doi:10.1007/s11164-020-04318-1 · Cited by 27 · see citing works
A New Variant of Mutational and Polymorphic Signatures in the ERG11 Gene of Fluconazole-Resistant Candida albicans
Odiba, A. S., Durojaye, O. A., Ezeonu, I. M., Mgbeahuruike, A. C., & Nwanguma, B. C. (2022) · Infection and Drug Resistance · doi:10.2147/idr.s360973 · Cited by 27 · see citing works
Design, synthesis and biological activity of hybrid antifungals derived from fluconazole and mebendazole
Ghobadi, E., Hashemi, S. M., Fakhim, H., Hosseini‐khah, Z., Badali, H., & Emami, S. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115146 · Cited by 27 · see citing works
Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling
Rodrigues, G. C. S., Maia, M. D. S., de Souza, T. A., Lima, E. D. O., dos Santos, L. E. C. G., Silva, S. L., da Silva, M. S., Barbosa‐Filho, J. M., Rodrigues-Junior, V. S., Scotti, L., et al. (2023) · Pathogens · doi:10.3390/pathogens12030449 · Cited by 27 · see citing works
Synthesis of 5-heptadecyl-4H-1,2,4-triazole incorporated indole moiety: Antiviral (SARS-CoV-2), antimicrobial, and molecular docking studies
Salam, H. A. A. E., Abo‐Salem, H. M., Kutkat, O., Abdel-aziz, M. S., Montaser, A. S., & El-Sawy, E. R. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.137517 · Cited by 27 · see citing works
Precise genome editing using a CRISPR-Cas9 method highlights the role of CoERG11 amino acid substitutions in azole resistance in Candida orthopsilosis
Morio, F., Lombardi, L., Binder, U., Logé, C., Robert, E., Grässle, D., Bodin, M., Lass‐Flörl, C., Butler, G., & Pape, P. L. (2019) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz204 · Cited by 27 · see citing works
Reactivity, bioactivity, and antileishmanial activity of dihydrosyrindine and syringine: Modelling, cytotoxicity, molecular docking, molecular dynamics, and MM-GBSA analyses
Khaoua, O. (2025) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2025.109183 · Cited by 26 · see citing works
Cytochrome P450 Enzymes as Drug Targets in Human Disease
Guengerich, F. P. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.123.001431 · Cited by 26 · see citing works
Self-citation
The Role of Ergosterol and Sphingolipids in the Localization and Activity of Candida albicans’ Multidrug Transporter Cdr1p and Plasma Membrane ATPase Pma1p
Urbanek, A. K., Muraszko, J., Derkacz, D., Łukaszewicz, M., Bernat, P., & Krasowska, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179975 · Cited by 25 · see citing works
Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi
Yin, W., Zhang, Y., Cui, H., Jiang, H., Liu, L., Zheng, Y., Wu, T., Zhao, L., Sun, Y., Su, X., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113740 · Cited by 25 · see citing works
Oteseconazole: First Approved Orally Bioavailable and Selective CYP51 Inhibitor for the Treatment of Patients with Recurrent Vulvovaginal Candidiasis
De, S. K. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230220130024 · Cited by 24 · see citing works

Heterologous expression and characterization of the sterol 14α-demethylase CYP51F1 from Candida albicans
Park, H., Lee, I., Chun, Y., Yun, C., Johnston, J. B., de Montellano, P. R. O., & Kim, D. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.02.002 · Cited by 25 · see citing works
Azole Binding Properties of Candida albicans Sterol 14-α Demethylase (CaCYP51)
Warrilow, A. G. S., Martel, C. M., Parker, J. E., Melo, N., Lamb, D. C., Nes, W. D., Kelly, D. E., & Kelly, S. L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00587-10 · Cited by 112 · see citing works
The R467K Amino Acid Substitution in Candida albicans Sterol 14α-Demethylase Causes Drug Resistance through Reduced Affinity
Lamb, D. C., Kelly, D. E., White, T. C., & Kelly, S. L. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.1.63-67.2000 · Cited by 133 · see citing works
Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors
Podust, L. M., Poulos, T. L., & Waterman, M. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061562898 · Cited by 534 · see citing works
Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans
Binjubair, F. A., Parker, J. E., Warrilow, A. G. S., Puri, K., Braidley, P. J., Tatar, E., Kelly, S. L., Kelly, D. E., & Simons, C. (2020) · ChemMedChem · doi:10.1002/cmdc.202000250 · Cited by 29 · see citing works

Authors: Hargrove, T. Y., Friggeri, L., Wawrzak, Z., Qi, A., Hoekstra, W. J., Schotzinger, R. J., York, J. D., Guengerich, F. P., & Lepesheva, G. I.
Affiliations: Vanderbilt University (US)
Northwestern University (US)
Viamet Pharmaceuticals (United States) (US)
Corresponding author: Lepesheva, Galina I.
ORCID: Wawrzak, Zdzislaw
York, John D.
Guengerich, F. Peter
Lepesheva, Galina I.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2017-04
Volume: 292
Issue: 16
Pages: 6728-6743
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m117.778308
PMC: PMC5399120
OpenAlex: W2593598577
Cited by: 444
References: 57
Citations by year: 2026: 67 · 2025: 82 · 2024: 49 · 2023: 64 · 2022: 55 · 2021: 30 · 2020: 39 · 2019: 25 · 2018: 24 · 2017: 9
FWCI: 21.04
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 1243 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01 GM067871)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Keywords: Candida albicans, sterol 14α-demethylase, CYP51, cytochrome P450, azole antifungals, posaconazole, oteseconazole, fluconazole, ketoconazole, voriconazole, itraconazole, miconazole, clotrimazole, fungal sterol biosynthesis, drug resistance, Candida krusei, Candida glabrata, X-ray crystal structure, ligand binding, antifungal drug design
MeSH terms: Animals, Antifungal Agents, Azoles, Candida albicans, Crystallization, Fungal Proteins, Heme, Humans, Kinetics, Ligands, Microbial Sensitivity Tests, Protein Binding, Protein Conformation, Protons, Sterols, Rats, Sterol 14-Demethylase

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Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

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