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image of Acetohydroxyacid Synthase (AHAS) as a Promising and Underexplored Target for the Development of New Antifungal Agents

Abstract

Introduction

Fungi are ubiquitous and play crucial ecological roles, but fungal infections pose serious threats to human, animal, and environmental health, with a significant economic and social burden. Current antifungal therapies face challenges, such as limited drugs, toxicity, and resistance, highlighting the urgent need for drugs with new mechanisms of action. The enzyme acetohydroxyacid synthase (AHAS) is a promising target, as it is involved in branched-chain amino acid biosynthesis, a pathway lacking in animals and already explored in herbicide development.

Methods

We conducted an integrative review covering the antifungal potential of known AHAS inhibitors and the development of novel inhibitors with antifungal activity within the PubMed, ScienceDirect, and Web of Science databases.

Results

A total of 590 articles were obtained, and after applying the inclusion and exclusion criteria, 17 articles were selected. The review identified commercial herbicides as potent AHAS inhibitors of plant and animal pathogenic fungi and to have a broad spectrum of antifungal activity against many species, such as , , , , and .

Discussion

Based on these results, several compounds were designed, synthesized, and evaluated as antifungal agents, showing promising inhibitory properties against fungal AHAS and growth. Structural features of AHAS from different organisms were also investigated to guide drug development.

Conclusion

Considering structural insights and experimental data, AHAS inhibitors showed promising profile as broad-spectrum antifungals, with low toxicity to humans and the environment, supporting a One Health approach to control fungal infections across human, animal, and environmental health.

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2026-01-31

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References

  1. Bahram M. Netherway T. Fungi as mediators linking organisms and ecosystems. FEMS Microbiol. Rev. 2022 46 2 fuab058 10.1093/femsre/fuab058 34919672
    [Google Scholar]
  2. Karunarathna S.C. Ashwath N. Jeewon R. Editorial: The potential of fungi for enhancing crops and forestry systems. Front. Microbiol. 2021 12 813051 10.3389/fmicb.2021.813051 35003047
    [Google Scholar]
  3. Case N.T. Gurr S.J. Fisher M.C. Blehert D.S. Boone C. Casadevall A. Chowdhary A. Cuomo C.A. Currie C.R. Denning D.W. Ene I.V. Fritz-Laylin L.K. Gerstein A.C. Gow N.A.R. Gusa A. Iliev I.D. James T.Y. Jin H. Kahmann R. Klein B.S. Kronstad J.W. Ost K.S. Peay K.G. Shapiro R.S. Sheppard D.C. Shlezinger N. Stajich J.E. Stukenbrock E.H. Taylor J.W. Wright G.D. Cowen L.E. Heitman J. Segre J.A. Fungal impacts on Earth’s ecosystems. Nature 2025 638 8049 49 57 10.1038/s41586‑024‑08419‑4 39910383
    [Google Scholar]
  4. Yuvaraj M. Ramasamy M. Yuvaraj M. Ramasamy M. Role of Fungi in Agriculture. Biostimulants in Plant. Science 2020 1 10.5772/intechopen.89718
    [Google Scholar]
  5. Wu B. Hussain M. Zhang W. Stadler M. Liu X. Xiang M. Current insights into fungal species diversity and perspective on naming the environmental DNA sequences of fungi. Mycology 2019 10 3 127 140 10.1080/21501203.2019.1614106 31448147
    [Google Scholar]
  6. Ascioglu S. Rex J.H. de Pauw B. Bennett J.E. Bille J. Crokaert F. Denning D.W. Donnelly J.P. Edwards J.E. Erjavec Z. Fiere D. Lortholary O. Maertens J. Meis J.F. Patterson T.F. Ritter J. Selleslag D. Shah P.M. Stevens D.A. Walsh T.J. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: An international consensus. Clin. Infect. Dis. 2002 34 1 7 14 10.1086/323335 11731939
    [Google Scholar]
  7. Peng Y. Li S.J. Yan J. Tang Y. Cheng J.P. Gao A.J. Yao X. Ruan J.J. Xu B.L. Research progress on phytopathogenic fungi and their role as biocontrol agents. Front. Microbiol. 2021 12 670135 10.3389/fmicb.2021.670135 34122383
    [Google Scholar]
  8. Salvatore M.M. Andolfi A. Phytopathogenic fungi and toxicity. Toxins 2021 13 10 689 10.3390/toxins13100689 34678983
    [Google Scholar]
  9. Dorigan A.F. Moreira S.I. da Silva Costa Guimarães S. Cruz-Magalhães V. Alves E. Target and non‐target site mechanisms of fungicide resistance and their implications for the management of crop pathogens. Pest Manag. Sci. 2023 79 12 4731 4753 10.1002/ps.7726 37592727
    [Google Scholar]
  10. Duke S.O. Pan Z. Bajsa-Hirschel J. Tamang P. Hammerschmidt R. Lorsbach B.A. Sparks T.C. Molecular targets of herbicides and fungicides—Are there useful overlaps for fungicide discovery? J. Agric. Food Chem. 2023 71 51 20532 20548 10.1021/acs.jafc.3c07166 38100716
    [Google Scholar]
  11. Xu J. Assessing global fungal threats to humans. mLife 2022 1 3 223 240 10.1002/mlf2.12036 38818220
    [Google Scholar]
  12. Fisher M.C. Gow N.A.R. Gurr S.J. Tackling emerging fungal threats to animal health, food security and ecosystem resilience. hilos. Trans R Soc. Lond B Biol. Sci 2016 371 1709 20160332 10.1098/rstb.2016.0332 28080997
    [Google Scholar]
  13. Fisher M.C. Henk D.A. Briggs C.J. Brownstein J.S. Madoff L.C. McCraw S.L. Gurr S.J. Emerging fungal threats to animal, plant and ecosystem health. Nature 2012 484 7393 186 194 10.1038/nature10947 22498624
    [Google Scholar]
  14. Taylor D.L. Hollingsworth T.N. McFarland J.W. Lennon N.J. Nusbaum C. Ruess R.W. A first comprehensive census of fungi in soil reveals both hyperdiversity and fine‐scale niche partitioning. Ecol. Monogr. 2014 84 1 3 20 10.1890/12‑1693.1
    [Google Scholar]
  15. Badiee P. Hashemizadeh Z. Opportunistic invasive fungal infections: Diagnosis & clinical management. Indian J. Med. Res. 2014 139 2 195 204 [PMID: 24718393
    [Google Scholar]
  16. Pagano L. Mayor S. Invasive fungal infections in high-risk patients: Report from TIMM-8 2017. Future Sci. OA 2018 4 6 FSO307 10.4155/fsoa‑2018‑0019 30057784
    [Google Scholar]
  17. Perlroth J. Choi B. Spellberg B. Nosocomial fungal infections: Epidemiology, diagnosis, and treatment. Med. Mycol. 2007 45 4 321 346 10.1080/13693780701218689 17510856
    [Google Scholar]
  18. Low C.Y. Rotstein C. Emerging fungal infections in immunocompromised patients. F1000 Med. Rep. 2011 3 14 10.3410/M3‑14 21876720
    [Google Scholar]
  19. Wanke B. Lazéra M.S. Nucci M. Fungal infections in the immunocompromised host. Mem. Inst. Oswaldo Cruz 2000 95 Suppl. 1 153 158 10.1590/S0074‑02762000000700025 11142705
    [Google Scholar]
  20. Brown G.D. Denning D.W. Gow N.A.R. Levitz S.M. Netea M.G. White T.C. Hidden killers: Human fungal infections. Sci. Transl. Med. 2012 4 165 165rv13 10.1126/scitranslmed.3004404 23253612
    [Google Scholar]
  21. Kainz K. Bauer M.A. Madeo F. Carmona-Gutierrez D. Fungal infections in humans: The silent crisis. Microb. Cell 2020 7 6 143 145 10.15698/mic2020.06.718 32548176
    [Google Scholar]
  22. Lockhart S.R. Guarner J. Emerging and reemerging fungal infections. Semin. Diagn. Pathol. 2019 36 3 177 181 10.1053/j.semdp.2019.04.010 31010605
    [Google Scholar]
  23. Bongomin F. Gago S. Oladele R. Denning D. Global and multi-national prevalence of fungal diseases—Estimate precision. J. Fungi 2017 3 4 57 10.3390/jof3040057 29371573
    [Google Scholar]
  24. Rayens E. Norris K.A. Prevalence and healthcare burden of fungal infections in the United States, 2018. Open Forum Infect. Dis. 2022 9 1 ofab593 10.1093/ofid/ofab593 35036461
    [Google Scholar]
  25. Fungal Disease frequency. 2025 Available from: https://gaffi.org/why/fungal-disease-frequency/
  26. Denning D.W. Global incidence and mortality of severe fungal disease. Lancet Infect. Dis. 2024 24 7 e428 e438 10.1016/S1473‑3099(23)00692‑8 38224705
    [Google Scholar]
  27. Brown G.D. Ballou E.R. Bates S. Bignell E.M. Borman A.M. Brand A.C. Brown A.J.P. Coelho C. Cook P.C. Farrer R.A. Govender N.P. Gow N.A.R. Hope W. Hoving J.C. Dangarembizi R. Harrison T.S. Johnson E.M. Mukaremera L. Ramsdale M. Thornton C.R. Usher J. Warris A. Wilson D. The pathobiology of human fungal infections. Nat. Rev. Microbiol. 2024 22 11 687 704 10.1038/s41579‑024‑01062‑w 38918447
    [Google Scholar]
  28. Weimer K.E.D. Smith P.B. Puia-Dumitrescu M. Aleem S. Invasive fungal infections in neonates: A review. Pediatr. Res. 2022 91 2 404 412 10.1038/s41390‑021‑01842‑7 34880444
    [Google Scholar]
  29. Benitez L.L. Carver P.L. Adverse effects associated with long-term administration of azole antifungal agents. Drugs 2019 79 8 833 853 10.1007/s40265‑019‑01127‑8 31093949
    [Google Scholar]
  30. Baxter C.G. Marshall A. Roberts M. Felton T.W. Denning D.W. Peripheral neuropathy in patients on long-term triazole antifungal therapy. J. Antimicrob. Chemother. 2011 66 9 2136 2139 10.1093/jac/dkr233 21685202
    [Google Scholar]
  31. Kyriakidis I. Tragiannidis A. Munchen S. Groll A.H. Clinical hepatotoxicity associated with antifungal agents. Expert Opin. Drug Saf. 2017 16 2 149 165 10.1080/14740338.2017.1270264 27927037
    [Google Scholar]
  32. Lestner J.M. Denning D.W. Tremor: A newly described adverse event with long-term itraconazole therapy. J. Neurol. Neurosurg. Psychiatry 2010 81 3 327 329 10.1136/jnnp.2009.174706 20185472
    [Google Scholar]
  33. Hazin R. Abuzetun J.Y. Suker M. Porter J. Rhabdomyolysis induced by simvastatin-fluconazole combination. J. Natl. Med. Assoc. 2008 100 4 444 446 10.1016/S0027‑9684(15)31280‑3 18481486
    [Google Scholar]
  34. Pana Z.D. Roilides E. Risk of azole‐enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: Old problem - New Dilemma. Pediatr. Blood Cancer 2011 57 1 30 35 10.1002/pbc.22972 21265011
    [Google Scholar]
  35. Kaur J. Nobile C.J. Antifungal drug-resistance mechanisms in Candida biofilms. Curr. Opin. Microbiol. 2023 71 102237 10.1016/j.mib.2022.102237 36436326
    [Google Scholar]
  36. Lockhart S.R. Iqbal N. Cleveland A.A. Farley M.M. Harrison L.H. Bolden C.B. Baughman W. Stein B. Hollick R. Park B.J. Chiller T. Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011. J. Clin. Microbiol. 2012 50 11 3435 3442 10.1128/JCM.01283‑12 22875889
    [Google Scholar]
  37. Perlin D.S. Rautemaa-Richardson R. Alastruey-Izquierdo A. The global problem of antifungal resistance: Prevalence, mechanisms, and management. Lancet Infect. Dis. 2017 17 12 e383 e392 10.1016/S1473‑3099(17)30316‑X 28774698
    [Google Scholar]
  38. Romero M. Messina F. Marin E. Arechavala A. Depardo R. Walker L. Negroni R. Santiso G. Antifungal resistance in clinical isolates of Aspergillus spp.: When local epidemiology breaks the norm. J. Fungi 2019 5 2 41 10.3390/jof5020041 31117260
    [Google Scholar]
  39. Shang Y. Xiao G. Zheng P. Cen K. Zhan S. Wang C. Divergent and convergent evolution of fungal pathogenicity. Genome Biol. Evol. 2016 8 5 1374 1387 10.1093/gbe/evw082 27071652
    [Google Scholar]
  40. Gerwick B.C. Subramanian M.V. Loney-Gallant V.I. Chandler D.P. Mechanism of action of the 1,2,4‐triazolo[1,5‐a] pyrimidines. Pestic. Sci. 1990 29 3 357 364 10.1002/ps.2780290310
    [Google Scholar]
  41. LaRossa R.A. Schloss J.V. The sulfonylurea herbicide sulfometuron methyl is an extremely potent and selective inhibitor of acetolactate synthase in Salmonella typhimurium. J. Biol. Chem. 1984 259 14 8753 8757 10.1016/S0021‑9258(17)47217‑6 6378902
    [Google Scholar]
  42. Shaner D.L. Anderson P.C. Stidham M.A. Imidazolinones: Potent inhibitors of acetohydroxyacid synthase. Plant Physiol. 1984 76 2 545 546 10.1104/pp.76.2.545 16663878
    [Google Scholar]
  43. Chipman D. Barak Z. Schloss J.V. Biosynthesis of 2-aceto-2-hydroxy acids: Acetolactate synthases and acetohydroxyacid synthases. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 1998 1385 2 401 419 10.1016/S0167‑4838(98)00083‑1 9655946
    [Google Scholar]
  44. Dumas R. Biou V. Halgand F. Douce R. Duggleby R.G. Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase. Acc. Chem. Res. 2001 34 5 399 408 10.1021/ar000082w 11352718
    [Google Scholar]
  45. Umbarger H.E. Brown B. Isoleucine and valine metabolism in Escherichia coli. VIII. The formation of acetolactate. J. Biol. Chem. 1958 233 5 1156 1160 10.1016/S0021‑9258(19)77358‑X 13598751
    [Google Scholar]
  46. Chipman D.M. Duggleby R.G. Tittmann K. Mechanisms of acetohydroxyacid synthases. Curr. Opin. Chem. Biol. 2005 9 5 475 481 10.1016/j.cbpa.2005.07.002 16055369
    [Google Scholar]
  47. Tittmann K. Golbik R. Uhlemann K. Khailova L. Schneider G. Patel M. Jordan F. Chipman D.M. Duggleby R.G. Hübner G. NMR analysis of covalent intermediates in thiamin diphosphate enzymes. Biochemistry 2003 42 26 7885 7891 10.1021/bi034465o 12834340
    [Google Scholar]
  48. Umbarger H.E. Biosynthesis of the branched-chain amino acids. Escherichia coli and Salmonella: Cellular and molecular biology. Washington, D.C. ASM Press 1996 442 457
    [Google Scholar]
  49. Sayers E.W. Bolton E.E. Brister J.R. Canese K. Chan J. Comeau D.C. Connor R. Funk K. Kelly C. Kim S. Madej T. Marchler-Bauer A. Lanczycki C. Lathrop S. Lu Z. Thibaud-Nissen F. Murphy T. Phan L. Skripchenko Y. Tse T. Wang J. Williams R. Trawick B.W. Pruitt K.D. Sherry S.T. Database resources of the national center for biotechnology information. Nucleic Acids Res. 2022 50 D1 D20 D26 10.1093/nar/gkab1112 34850941
    [Google Scholar]
  50. Costelloe S.J. Ward J.M. Dalby P.A. Evolutionary analysis of the TPP-dependent enzyme family. J. Mol. Evol. 2008 66 1 36 49 10.1007/s00239‑007‑9056‑2 18043855
    [Google Scholar]
  51. Chang Y.Y. Cronan J.E. Common ancestry of Escherichia coli pyruvate oxidase and the acetohydroxy acid synthases of the branched-chain amino acid biosynthetic pathway. J. Bacteriol. 1988 170 9 3937 3945 10.1128/jb.170.9.3937‑3945.1988 3045082
    [Google Scholar]
  52. Duggleby R.G. Domain relationships in thiamine diphosphate-dependent enzymes. Acc. Chem. Res. 2006 39 8 550 557 10.1021/ar068022z 16906751
    [Google Scholar]
  53. Li W. Cowley A. Uludag M. Gur T. McWilliam H. Squizzato S. Park Y.M. Buso N. Lopez R. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic Acids Res. 2015 43 W1 W580 W584 10.1093/nar/gkv279 25845596
    [Google Scholar]
  54. McWilliam H. Li W. Uludag M. Squizzato S. Park Y.M. Buso N. Cowley A.P. Lopez R. Analysis tool web services from the EMBL-EBI. Nucleic Acids Res. 2013 41 W1 W597 W600 10.1093/nar/gkt376 23671338
    [Google Scholar]
  55. Sievers F. Wilm A. Dineen D. Gibson T.J. Karplus K. Li W. Lopez R. McWilliam H. Remmert M. Söding J. Thompson J.D. Higgins D.G. Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 2011 7 1 539 10.1038/msb.2011.75 21988835
    [Google Scholar]
  56. Guex N. Peitsch M.C. SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling. Electrophoresis 1997 18 15 2714 2723 10.1002/elps.1150181505 9504803
    [Google Scholar]
  57. Pang S.S. Guddat L.W. Duggleby R.G. Crystallization of the catalytic subunit of Saccharomyces cerevisiae acetohydroxyacid synthase. Acta Crystallogr. D Biol. Crystallogr. 2001 57 9 1321 1323 10.1107/S0907444901011635 11526332
    [Google Scholar]
  58. Pang S.S. Duggleby R.G. Schowen R.L. Guddat L.W. The crystal structures of Klebsiella pneumoniae acetolactate synthase with enzyme-bound cofactor and with an unusual intermediate. J. Biol. Chem. 2004 279 3 2242 2253 10.1074/jbc.M304038200 14557277
    [Google Scholar]
  59. Pang S.S. Guddat L.W. Duggleby R.G. Crystallization of Arabidopsis thaliana acetohydroxyacid synthase in complex with the sulfonylurea herbicide chlorimuron ethyl. Acta Crystallogr. D Biol. Crystallogr. 2004 60 1 153 155 10.1107/S0907444903025423 14684914
    [Google Scholar]
  60. McCourt J.A. Pang S.S. Guddat L.W. Duggleby R.G. Elucidating the specificity of binding of sulfonylurea herbicides to acetohydroxyacid synthase. Biochemistry 2005 44 7 2330 2338 10.1021/bi047980a 15709745
    [Google Scholar]
  61. Niu X. Liu X. Zhou Y. Niu C. Xi Z. Su X.D. Preliminary X-ray crystallographic studies of the catalytic subunit of Escherichia coli AHAS II with its cofactors. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2011 67 6 659 661 10.1107/S1744309111008839 21636904
    [Google Scholar]
  62. Pang S.S. Guddat L.W. Duggleby R.G. Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase. J. Biol. Chem. 2003 278 9 7639 7644 10.1074/jbc.M211648200 12496246
    [Google Scholar]
  63. Pang S.S. Duggleby R.G. Guddat L.W. Crystal structure of yeast acetohydroxyacid synthase: A target for herbicidal inhibitors. J. Mol. Biol. 2002 317 2 249 262 10.1006/jmbi.2001.5419 11902841
    [Google Scholar]
  64. Garcia M.D. Nouwens A. Lonhienne T.G. Guddat L.W. Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families. Proc. Natl. Acad. Sci. USA 2017 114 7 E1091 E1100 10.1073/pnas.1616142114 28137884
    [Google Scholar]
  65. Chaleff R.S. Mauvais C.J. Acetolactate synthase is the site of action of two sulfonylurea herbicides in higher plants. Science 1984 224 4656 1443 1445 10.1126/science.224.4656.1443 17793381
    [Google Scholar]
  66. Namgoong S.K. Lee H.J. Kim Y.S. Shin J.H. Che J.K. Jang D.Y. Kim G.S. Yoo J.W. Kang M.K. Kil M.W. Choi J.D. Chang S.I. Synthesis of the quinoline-linked triazolopyrimidine analogues and their interactions with the recombinant tobacco acetolactate synthase. Biochem. Biophys. Res. Commun. 1999 258 3 797 801 10.1006/bbrc.1999.0708 10329466
    [Google Scholar]
  67. Los M.O.O. O-(5-Oxo-2-Imidazolin-2-Yl)Arylcarboxylates: A new class of herbicides. In: Pesticide Synthesis Through Rational Approaches; American Chemical Society 1984 255 29 40
    [Google Scholar]
  68. Lee Y.T. Cui C.J. Chow E.W.L. Pue N. Lonhienne T. Wang J.G. Fraser J.A. Guddat L.W. Sulfonylureas have antifungal activity and are potent inhibitors of Candida albicans acetohydroxyacid synthase. J. Med. Chem. 2013 56 1 210 219 10.1021/jm301501k 23237384
    [Google Scholar]
  69. Garcia M.D. Chua S.M.H. Low Y.S. Lee Y.T. Agnew-Francis K. Wang J.G. Nouwens A. Lonhienne T. Williams C.M. Fraser J.A. Guddat L.W. Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections. Proc. Natl. Acad. Sci. USA 2018 115 41 E9649 E9658 10.1073/pnas.1809422115 30249642
    [Google Scholar]
  70. Low Y.S. Garcia M.D. Lonhienne T. Fraser J.A. Schenk G. Guddat L.W. Triazolopyrimidine herbicides are potent inhibitors of Aspergillus fumigatus acetohydroxyacid synthase and potential antifungal drug leads. Sci. Rep. 2021 11 1 21055 10.1038/s41598‑021‑00349‑9 34702838
    [Google Scholar]
  71. Agnew-Francis K.A. Tang Y. Lin X. Low Y.S. Wun S.J. Kuo A. Elias S.M.A.S.I. Lonhienne T. Condon N.D. Pimentel B.N.A.S. Vergani C.E. Smith M.T. Fraser J.A. Williams C.M. Guddat L.W. Herbicides that target acetohydroxyacid synthase are potent inhibitors of the growth of drug-resistant Candida auris. ACS Infect. Dis. 2020 6 11 2901 2912 10.1021/acsinfecdis.0c00229 32986949
    [Google Scholar]
  72. Duggleby R.G. Pang S.S. Yu H. Guddat L.W. Systematic characterization of mutations in yeast acetohydroxyacid synthase. Eur. J. Biochem. 2003 270 13 2895 2904 10.1046/j.1432‑1033.2003.03671.x 12823560
    [Google Scholar]
  73. Sanglard D. Coste A. Ferrari S. Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation. FEMS Yeast Res. 2009 9 7 1029 1050 10.1111/j.1567‑1364.2009.00578.x 19799636
    [Google Scholar]
  74. Morales-López S.E. Parra-Giraldo C.M. Ceballos-Garzón A. Martínez H.P. Rodríguez G.J. Álvarez-Moreno C.A. Rodríguez J.Y. Invasive infections with multidrug-resistant yeast Candida auris, Colombia. Emerg. Infect. Dis. 2017 23 1 162 164 10.3201/eid2301.161497 27983941
    [Google Scholar]
  75. Satoh K. Makimura K. Hasumi Y. Nishiyama Y. Uchida K. Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol. Immunol. 2009 53 1 41 44 10.1111/j.1348‑0421.2008.00083.x 19161556
    [Google Scholar]
  76. Ruiz-Gaitán A. Martínez H. Moret A.M. Calabuig E. Tasias M. Alastruey-Izquierdo A. Zaragoza Ó. Mollar J. Frasquet J. Salavert-Lletí M. Ramírez P. López-Hontangas J.L. Pemán J. Detection and treatment of Candida auris in an outbreak situation: Risk factors for developing colonization and candidemia by this new species in critically ill patients. Expert Rev. Anti Infect. Ther. 2019 17 4 295 305 10.1080/14787210.2019.1592675 30922129
    [Google Scholar]
  77. Romera D. Aguilera-Correa J.J. Gadea I. Viñuela-Sandoval L. García-Rodríguez J. Esteban J. Candida auris: A comparison between planktonic and biofilm susceptibility to antifungal drugs. J. Med. Microbiol. 2019 68 9 1353 1358 10.1099/jmm.0.001036 31271350
    [Google Scholar]
  78. Short B. Brown J. Delaney C. Sherry L. Williams C. Ramage G. Kean R. Candida auris exhibits resilient biofilm characteristics in vitro: Implications for environmental persistence. J. Hosp. Infect. 2019 103 1 92 96 10.1016/j.jhin.2019.06.006 31226270
    [Google Scholar]
  79. Lonhienne T. Garcia M.D. Pierens G. Mobli M. Nouwens A. Guddat L.W. Structural insights into the mechanism of inhibition of AHAS by herbicides. Proc. Natl. Acad. Sci. USA 2018 115 9 E1945 E1954 10.1073/pnas.1714392115 29440497
    [Google Scholar]
  80. Lonhienne T. Nouwens A. Williams C.M. Fraser J.A. Lee Y.T. West N.P. Guddat L.W. Commercial herbicides can trigger the oxidative inactivation of acetohydroxyacid synthase. Angew. Chem. Int. Ed. 2016 55 13 4247 4251 10.1002/anie.201511985 26924714
    [Google Scholar]
  81. McCourt J.A. Pang S.S. King-Scott J. Guddat L.W. Duggleby R.G. Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase. Proc. Natl. Acad. Sci. USA 2006 103 3 569 573 10.1073/pnas.0508701103 16407096
    [Google Scholar]
  82. Shishodia S.K. Tiwari S. Shankar J. Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology 2019 10 3 151 165 10.1080/21501203.2019.1574927 31448149
    [Google Scholar]
  83. Richie D.L. Thompson K.V. Studer C. Prindle V.C. Aust T. Riedl R. Estoppey D. Tao J. Sexton J.A. Zabawa T. Drumm J. Cotesta S. Eichenberger J. Schuierer S. Hartmann N. Movva N.R. Tallarico J.A. Ryder N.S. Hoepfner D. Identification and evaluation of novel acetolactate synthase inhibitors as antifungal agents. Antimicrob. Agents Chemother. 2013 57 5 2272 2280 10.1128/AAC.01809‑12 23478965
    [Google Scholar]
  84. Bélai I. Oros G. Responses of different fungal and plant species to acetolactate synthase inhibitors and their derivatives. J. Environ. Sci. Health B 1996 31 3 615 620 10.1080/03601239609373027
    [Google Scholar]
  85. Chen W. Li Y. Shi Y. Wei W. Chen Y. Li Y. Liu J. Li B. Li Z. Synthesis and evaluation of novel N-(4′-arylpyrimidin-2′-yl) sulfonylurea derivatives as potential antifungal agents. Chem. Res. Chin. Univ. 2015 31 2 218 223 10.1007/s40242‑015‑4362‑5
    [Google Scholar]
  86. Wei W. Cheng D. Chen W. Liu J. Wan Y. Li Y. Li Y. Yu S. Li Z. Design, syntheses and biological activities of novel sulfonylureas containing an oxime ether moiety. Chem. Res. Chin. Univ. 2016 32 2 195 201 10.1007/s40242‑016‑5406‑1
    [Google Scholar]
  87. Ramudu D.B.J. Babu P.H. Venkateswarlu N. Vijaya T. Rasheed S. Raju C.N. Chalapathi P.V. Sulfonylurea derivatives of tolbutamide analogues: Synthesis and evaluation of antimicrobial and antioxidant activities. Indian J. Chem. 2018 57 127 135
    [Google Scholar]
  88. Chen W. Li Y. Zhou Y. Ma Y. Li Z. Design, synthesis and SAR study of novel sulfonylurea derivatives containing arylpyrimidine moieties as potential anti-phytopathogenic fungal agents. Chin. Chem. Lett. 2019 30 12 2160 2162 10.1016/j.cclet.2019.04.072
    [Google Scholar]
  89. Wu R.J. Zhou K.X. Yang H. Song G.Q. Li Y.H. Fu J.X. Zhang X. Yu S.J. Wang L.Z. Xiong L.X. Niu C.W. Song F.H. Yang H. Wang J.G. Chemical synthesis, crystal structure, versatile evaluation of their biological activities and molecular simulations of novel pyrithiobac derivatives. Eur. J. Med. Chem. 2019 167 472 484 10.1016/j.ejmech.2019.02.002 30784880
    [Google Scholar]
  90. Wu R.J. Ren T. Gao J.Y. Wang L. Yu Q. Yao Z. Song G.Q. Ruan W.B. Niu C.W. Song F.H. Zhang L.X. Li M. Wang J.G. Chemical preparation, biological evaluation and 3D-QSAR of ethoxysulfuron derivatives as novel antifungal agents targeting acetohydroxyacid synthase. Eur. J. Med. Chem. 2019 162 348 363 10.1016/j.ejmech.2018.11.005 30448420
    [Google Scholar]
  91. Meng F. Mi P. Yu Z. Wei W. Gao L. Ren J. Li Z. Dai H. Design, synthesis and biological evaluation of 5 substituted sulfonylureas as novel antifungal agents targeting acetohydroxyacid synthase. J. Mol. Struct. 2022 1260 132756 10.1016/j.molstruc.2022.132756
    [Google Scholar]
  92. Shang M.H. Zhang K. Zhang J.S. Niu C.W. Li Y.H. Song F.H. Wang J.G. Chemical synthesis, biological activities, and molecular simulations of novel sulfonylurea compounds bearing ortho ‐alkoxy substitutions. Chem. Biol. Drug Des. 2022 100 4 487 501 10.1111/cbdd.14114 35792871
    [Google Scholar]
  93. Sun X.W. Liu Y. Wang X. Li H.R. Lin X. Tang J.Y. Xu Q. Agnew-Francis K.A. Fraser J.A. Sun Z.J. Guddat L.W. Wang J.G. Structure-activity relationships of bensulfuron methyl and its derivatives as novel agents against drug‐resistant Candida auris. Chem. Biol. Drug Des. 2024 103 1 14364 10.1111/cbdd.14364 37806947
    [Google Scholar]
  94. Lowes D.J. Miao J. Al-waqfi R.A. Avad K.A. Hevener K.E. Peters B.M. Identification of dual-target compounds with antifungal and Anti-NLRP3 inflammasome activity. ACS Infect. Dis. 2021 7 8 2522 2535 10.1021/acsinfecdis.1c00270 34260210
    [Google Scholar]
  95. Bouria H. Alliouche H. Chouiter M.I. Bouraiou A. Merazig H. Silva A.M.S. Belfaitah A. Synthesis, characterization of new α‐quinolin‐3‐yl‐α‐(aminoamides, aminoesters) and bi ‐heterocyclic aromatic systems from gem ‐dicyanoepoxides and their pharmacological activity as antioxidant and antifungal agents. J. Heterocycl. Chem. 2023 60 10 1778 1792 10.1002/jhet.4720
    [Google Scholar]
  96. Macit A.Z. Hasanoğlu Özkan E. Ogutcu H. Nartop D. Synthesis and in vitro antimicrobial evaluation of novel potent bioactive heterocyclic compounds. Polycycl. Aromat. Compd. 2024 44 10 6862 6873 10.1080/10406638.2023.2298863
    [Google Scholar]
  97. Bhargava A. Klamer K. Sharma M. Ortiz D. Saravolatz L. Candida auris: A continuing threat. Microorganisms 2025 13 3 652 10.3390/microorganisms13030652 40142543
    [Google Scholar]
  98. Marena G.D. Thomaz L. Nosanchuk J.D. Taborda C.P. Galleria mellonella as an invertebrate model for studying fungal infections. J. Fungi 2025 11 2 157 10.3390/jof11020157 39997451
    [Google Scholar]
  99. Wang C. Yang G.Y. Wei Y.L. Li S.Q. Li H.Y. Xia Z.W. Yang L.L. He X.L. Zhang Y.Y. Ren D. Chen T.Z. Qian S. Wang Z.Y. Design, synthesis, and bioevaluation of sulfonylamides as acetohydroxyacid synthase inhibitors. J. Mol. Struct. 2025 1326 141075 10.1016/j.molstruc.2024.141075
    [Google Scholar]
  100. Niu Y. Wu Z. Hu Q. Wu Y. Jiang Q. Yang X. Discovery of acetohydroxyacid synthase inhibitors as anti-tuberculosis lead compounds from natural products. Bioorg. Med. Chem. 2025 118 118041 10.1016/j.bmc.2024.118041 39708691
    [Google Scholar]
  101. Wun S.J. Tan L. Lonhienne T.G. Low Y.S. Josh P. Kuo A. Smith M.T. Gao Y. Pierens G.K. Guddat L.W. West N.P. Florasulam is a potent inhibitor of Mycobacterium tuberculosis acetohydroxyacid synthase and possesses in vivo antituberculosis activity. ACS Infect. Dis. 2025 11 5 1180 1189 10.1021/acsinfecdis.4c01028 40214257
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266434047251126045111
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Acetohydroxyacid Synthase (AHAS) as a Promising and Underexplored Target for the Development of New Antifungal Agents
Bentham Science Publishers ; https://doi.org/10.2174/0115680266434047251126045111
/content/journals/ctmc/10.2174/0115680266434047251126045111
/content/journals/ctmc/10.2174/0115680266434047251126045111
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  • Article Type:     Review Article
Keywords: Inhibitor ; Fungicide ; Herbicides ; Acetolactate synthase ; Antifungal ; Acetohydroxyacid synthase ; Drug discovery

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