Skip to content
2000
image of Exploring the Carbonic Anhydrase Activation Properties of 4-arylazo-3,5-diamino-1H-pyrazoles against hCA I, II, IV, and VII isoenzymes

Abstract

Introduction

CAs serve as crucial enzymes involved in a variety of physiological processes, including brain metabolism and cognitive function. hCA VII, a brain-associated isoform, plays an important role in modulating cerebral metabolism. Activating hCA VII may provide therapeutic benefits in Alzheimer's disease and other neurodegenerative or age-related illnesses. This study proposes to add to the growing interest in CAAs by developing innovative drugs with selective activation characteristics that target brain-associated CA isoforms.

Methods

A series of 4-arylazo-3,5-diamino-1H-pyrazoles have been produced by reacting aniline and aniline derivatives with a malononitrile solution at 0-5 °C, resulting in compounds . Then, arylazo malononitrile compounds were added with hydrazine monohydrate to obtain 4-arylazo-3,5-diamino-1H-pyrazole derivatives . The activity of the synthesized compounds was examined on human CA isoforms I, II, IV, and VII to determine activation potency and selectivity.

Results

The synthesized compounds demonstrated a wide spectrum of strong micromolar activation on human CA isoforms, with particularly encouraging results for hCA VII. The discovered activators showed a high selectivity profile for the brain-associated hCA VII isoform, indicating their potential use in neurological methods of therapy.

Discussion

Among the most compelling findings of this study is the unprecedented potency of several synthesized derivatives, particularly and in selectively activating hCA VII far beyond the benchmark histamine, positioning them as promising pharmacological candidates for addressing CA-related neurological disorders.

Conclusion

The research successfully discovered potent and selective CAAs with specific activity against hCA VII, a key enzyme in brain metabolism. These outcomes offer novel possibilities for developing medicinal products for neurological disorders and provide critical molecules for further study into CAAs. Furthermore, the study advances our understanding of enzyme activation kinetics and gives significant insights into the future of enzyme-based treatment research.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266373008250723064558
2025-07-28
2025-09-13

  • From This Site

    /content/journals/ctmc/10.2174/0115680266373008250723064558
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Supuran C.T. A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation. Bioorg. Med. Chem. Lett. 2023 93 129411 10.1016/j.bmcl.2023.129411 37507055
    [Google Scholar]
  2. Kumar A. Siwach K. Supuran C.T. Sharma P.K. A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors. Bioorg. Chem. 2022 126 105920 10.1016/j.bioorg.2022.105920 35671645
    [Google Scholar]
  3. De Simone G. Alterio V. Supuran C.T. Exploiting the hydrophobic and hydrophilic binding sites for designing carbonic anhydrase inhibitors. Expert Opin. Drug Discov. 2013 8 7 793 810 10.1517/17460441.2013.795145 23627619
    [Google Scholar]
  4. Neri D. Supuran C.T. Interfering with pH regulation in tumours as a therapeutic strategy. Nat. Rev. Drug Discov. 2011 10 10 767 777 10.1038/nrd3554 21921921
    [Google Scholar]
  5. Supuran C.T. Carbonic anhydrase inhibitors. Bioorg. Med. Chem. Lett. 2010 20 12 3467 3474 10.1016/j.bmcl.2010.05.009 20529676
    [Google Scholar]
  6. a Mishra K.M.A. Sethi K.K. Unveiling tomorrow: Carbonic anhydrase activators and inhibitors pioneering new frontiers in Alzheimer’s disease.Activation of α-, β-, γ- δ-, ζ- and η- class of carbonic anhydrases with amines and amino acids: A review. Arch. Pharm. (Weinheim). J. Enzyme Inhib. Med. Chem. 2025 358 1 e2400748 10.1002/ardp.202400748 39506506
    [Google Scholar]
  7. b Akocak S. Supuran C.T. Unveiling tomorrow: Carbonic anhydrase activators and inhibitors pioneering new frontiers in Alzheimer’s disease.Activation of α-, β-, γ- δ-, ζ- and η- class of carbonic anhydrases with amines and amino acids: A review. Arch. Pharm. (Weinheim). J. Enzyme Inhib. Med. Chem. 2019 34 1 1652 1659 10.1080/14756366.2019.1664501 31530034
    [Google Scholar]
  8. Supuran C.T. Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 2008 7 2 168 181 10.1038/nrd2467 18167490
    [Google Scholar]
  9. Supuran C.T. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin. Drug Discov. 2017 12 1 61 88 10.1080/17460441.2017.1253677 27783541
    [Google Scholar]
  10. Andring J.T. Fouch M. Akocak S. Angeli A. Supuran C.T. Ilies M.A. McKenna R. Structural basis of nanomolar inhibition of tumor-associated carbonic anhydrase IX: X-ray crystallographic and inhibition study of lipophilic inhibitors with acetazolamide backbone. J. Med. Chem. 2020 63 21 13064 13075 10.1021/acs.jmedchem.0c01390 33085484
    [Google Scholar]
  11. Supuran C.T. How many carbonic anhydrase inhibition mechanisms exist? J. Enzyme Inhib. Med. Chem. 2016 31 3 345 360 10.3109/14756366.2015.1122001 26619898
    [Google Scholar]
  12. Shabana A.M. Mondal U.K. Alam M.R. Spoon T. Ross C.A. Madesh M. Supuran C.T. Ilies M.A. pH-Sensitive multiligand gold nanoplatform targeting carbonic anhydrase IX enhances the delivery of doxorubicin to hypoxic tumor spheroids and overcomes the hypoxia-induced chemoresistance. ACS Appl. Mater. Interfaces 2018 10 21 17792 17808 10.1021/acsami.8b05607 29733576
    [Google Scholar]
  13. Akocak S. Güzel-Akdemir Ö. Kishore Kumar Sanku R. Russom S.S. Iorga B.I. Supuran C.T. Ilies M.A. Pyridinium derivatives of 3-aminobenzenesulfonamide are nanomolar-potent inhibitors of tumor-expressed carbonic anhydrase isozymes CA IX and CA XII. Bioorg. Chem. 2020 103 August 104204 10.1016/j.bioorg.2020.104204 32891000
    [Google Scholar]
  14. a Akocak S. Lolak N. Giovannuzzi S. Supuran C.T. Potent and Selective Carbonic Anhydrase Inhibition Activities of Pyrazolones Bearing Benzenesulfonamides. Bioorg. Med. Chem. Lett. 2023 95 August 129479 10.1016/j.bmcl.2023.129479
    [Google Scholar]
  15. b Yapar G. Lolak N. Bonardi A. Akocak S. Supuran C.T. Exploring the potency of diazo-coumarin containing hybrid molecules: Selective inhibition of tumor-associated carbonic anhydrase isoforms IX and XII. ChemMedChem 2024 19 4 e202300626 10.1002/cmdc.202300626
    [Google Scholar]
  16. c Dogan A. Yanilmaz E.M.B. Karakoc G. Parlar A. Annac E. Lolak N. Akocak S. Investigating the Anti-Inflammatory Potential of SLC-0111: A Carbonic Anhydrase Inhibitor Targeting Cyclooxygenase-Mediated Inflammatory Pathways in a Carrageenan-Induced Rat Model. J. Biochem. Mol. Toxicol. 2025 39 3 e70217 10.1002/jbt.70217
    [Google Scholar]
  17. Tekeli T. Akocak S. Petreni A. Lolak N. Çete S. Supuran C.T. Potent carbonic anhydrase I, II, IX and XII inhibition activity of novel primary benzenesulfonamides incorporating bis-ureido moieties. J. Enzyme Inhib. Med. Chem. 2023 38 1 2185762 10.1080/14756366.2023.2185762 36880350
    [Google Scholar]
  18. Carta F. Supuran C.T. Scozzafava A. Novel therapies for glaucoma: A patent review 2007 - 2011. Expert Opin. Ther. Pat. 2012 22 1 79 88 10.1517/13543776.2012.649006 22191414
    [Google Scholar]
  19. Mincione F. Nocentini A. Supuran C.T. Advances in the discovery of novel agents for the treatment of glaucoma. Expert Opin. Drug Discov. 2021 16 10 1209 1225 10.1080/17460441.2021.1922384 33914670
    [Google Scholar]
  20. Supuran C.T. Latest advances in specific inhibition of tumor-associated carbonic anhydrases. Future Med. Chem. 2023 15 1 5 7 10.4155/fmc‑2022‑0249 36636980
    [Google Scholar]
  21. Supuran C.T. Exploring the multiple binding modes of inhibitors to carbonic anhydrases for novel drug discovery. Expert Opin. Drug Discov. 2020 15 6 671 686 10.1080/17460441.2020.1743676 32208982
    [Google Scholar]
  22. Oguz M. Kalay E. Akocak S. Nocentini A. Lolak N. Boga M. Yilmaz M. Supuran C.T. Synthesis of calix[4]azacrown substituted sulphonamides with antioxidant, acetylcholinesterase, butyrylcholinesterase, tyrosinase and carbonic anhydrase inhibitory action. J. Enzyme Inhib. Med. Chem. 2020 35 1 1215 1223 10.1080/14756366.2020.1765166 32401067
    [Google Scholar]
  23. Mishra C.B. Tiwari M. Supuran C.T. Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today? Med. Res. Rev. 2020 40 6 2485 2565 10.1002/med.21713 32691504
    [Google Scholar]
  24. Zamanova S. Shabana A.M. Mondal U.K. Ilies M.A. Carbonic anhydrases as disease markers. Expert Opin. Ther. Pat. 2019 29 7 509 533 10.1080/13543776.2019.1629419 31172829
    [Google Scholar]
  25. Poggetti V. Salerno S. Baglini E. Barresi E. Da Settimo F. Taliani S. Carbonic anhydrase activators for neurodegeneration: An overview. Molecules 2022 27 8 2544 10.3390/molecules27082544 35458743
    [Google Scholar]
  26. Supuran C.T. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin. Ther. Pat. 2018 28 10 713 721 10.1080/13543776.2018.1519023 30175635
    [Google Scholar]
  27. Guglielmi P. Carradori S. Campestre C. Poce G. Novel therapies for glaucoma: A patent review (2013-2019). Expert Opin. Ther. Pat. 2019 29 10 769 780 10.1080/13543776.2019.1653279 31385719
    [Google Scholar]
  28. a Sun M.K. Alkon D.L. Carbonic anhydrase gating of attention: Memory therapy and enhancement.Carbonic anhydrase activators. 3: structure-activity correlations for a series of isozyme II activators. Trends Pharmacol. Sci. J. Pharm. Sci. 2002 23 2 83 89 10.1016/S0165‑6147(02)01899‑0 11830265
    [Google Scholar]
  29. b Clare B.W. Supuran C.T. Carbonic anhydrase gating of attention: Memory therapy and enhancement.Carbonic anhydrase activators. 3: structure-activity correlations for a series of isozyme II activators. Trends Pharmacol. Sci. J. Pharm. Sci. 1994 83 6 768 773 10.1002/jps.2600830603 9120804
    [Google Scholar]
  30. Sun M.K. Alkon D.L. Pharmacological enhancement of synaptic efficacy, spatial learning, and memory through carbonic anhydrase activation in rats. J. Pharmacol. Exp. Ther. 2001 297 3 961 967 10.1016/S0022‑3565(24)29621‑X 11356917
    [Google Scholar]
  31. a Supuran C.T. Carbonic Anhydrase Activators. Future Medicinal Chemistry. 2018 61 573 10.4155/fmc‑2017‑0223
    [Google Scholar]
  32. b Nocentini A. Costa A. Bonardi A. Ammara A. Giovannuzzi S. Petreni A. Bartolucci G. Rani B. Leri M. Bucciantini M. Fernandez-Bolanos J.G. Passani M.B. Provensi G. Gratteri P. Supuran C.T. Enhanced Recognition Memory through Dual Modulation of Brain Carbonic Anhydrases and Cholinesterases. J. Med. Chem. 2024 67 18 16873 16898 [https://doi.org/10.1021/acs.jmedchem.4c01866
    [Google Scholar]
  33. Supuran C.T. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin. Ther. Pat. 2018 28 10 709 712 10.1080/13543776.2018.1523897 30217119
    [Google Scholar]
  34. Rami M. Winum J.Y. Supuran C.T. Melnyk P. Yous S. (Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators. J. Enzyme Inhib. Med. Chem. 2019 34 1 224 229 10.1080/14756366.2018.1543292 30734616
    [Google Scholar]
  35. Akocak S. Lolak N. Bua S. Nocentini A. Supuran C.T. Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives. J. Enzyme Inhib. Med. Chem. 2019 34 1 1193 1198 10.1080/14756366.2019.1630616 31237157
    [Google Scholar]
  36. Vistoli G. Aldini G. Fumagalli L. Dallanoce C. Angeli A. Supuran C.T. Activation effects of Carnosine- and histidine-containing dipeptides on human carbonic anhydrases: A comprehensive study. Int. J. Mol. Sci. 2020 21 5 1761 10.3390/ijms21051761 32143488
    [Google Scholar]
  37. Akocak S. Lolak N. Bua S. Nocentini A. Karakoc G. Supuran C.T. α-Carbonic anhydrases are strongly activated by spinaceamine derivatives. Bioorg. Med. Chem. 2019 27 5 800 804 10.1016/j.bmc.2019.01.017 30683554
    [Google Scholar]
  38. Draghici B. Vullo D. Akocak S. Walker E.A. Supuran C.T. Ilies M.A. Ethylene bis-imidazoles are highly potent and selective activators for isozymes VA and VII of carbonic anhydrase, with a potential nootropic effect. Chem. Commun. (Camb.) 2014 50 45 5980 5983 10.1039/C4CC02346C 24763985
    [Google Scholar]
  39. Akocak S. Lolak N. Vullo D. Durgun M. Supuran C.T. Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators. J. Enzyme Inhib. Med. Chem. 2017 32 1 1305 1312 10.1080/14756366.2017.1386660 29072105
    [Google Scholar]
  40. Karrouchi K. Radi S. Ramli Y. Taoufik J. Mabkhot Y.N. Al-aizari F.A. Ansar M. Synthesis and pharmacological activities of pyrazole derivatives: A review. Molecules 2018 23 1 134 10.3390/molecules23010134 29329257
    [Google Scholar]
  41. Faria J.V. Vegi P.F. Miguita A.G.C. dos Santos M.S. Boechat N. Bernardino A.M.R. Recently reported biological activities of pyrazole compounds. Bioorg. Med. Chem. 2017 25 21 5891 10.1016/j.bmc.2017.09.035
    [Google Scholar]
  42. Sribalan R. Banuppriya G. Kirubavathi M. Jayachitra A. Padmini V. Multiple biological activities and molecular docking studies of newly synthesized 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcone hybrids. Bioorg. Med. Chem. Lett. 2016 26 23 5624 5630 10.1016/j.bmcl.2016.10.075 27825544
    [Google Scholar]
  43. Stauffer S.R. Coletta C.J. Tedesco R. Nishiguchi G. Carlson K. Sun J. Katzenellenbogen B.S. Katzenellenbogen J.A. Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-α-selective agonists. J. Med. Chem. 2000 43 26 4934 4947 10.1021/jm000170m 11150164
    [Google Scholar]
  44. Sayed G.H. Azab M.E. Anwer K.E. Raouf M.A. Negm N.A. Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications. J. Mol. Liq. 2018 252 329 338 10.1016/j.molliq.2017.12.156
    [Google Scholar]
  45. Abdel-Aal M.T. Abdel-Aleem A.A.H. Ibahim L.I. Zein A.L. Synthesis and antimicrobial activity of novel 5-amino-4-cyano-1H-pyrazole and quinazolin-4(3H)-one derivatives. Arch. Pharm. Res. 2010 33 12 1891 1900 10.1007/s12272‑010‑1202‑5 21191752
    [Google Scholar]
  46. Qiao L. Zhai Z.W. Cai P.P. Tan C.X. Weng J.Q. Han L. Liu X.H. Zhang Y.G. Synthesis, crystal structure, antifungal activity, and docking study of difluoromethyl pyrazole derivatives. J. Heterocycl. Chem. 2019 56 9 2536 2541 10.1002/jhet.3648
    [Google Scholar]
  47. Jorda R. Schütznerová E. Cankař P. Brychtová V. Navrátilová J. Kryštof V. Novel arylazopyrazole inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. 2015 23 9 1975 1981 10.1016/j.bmc.2015.03.025 25835357
    [Google Scholar]
  48. Ismail M.M.F. Soliman D.H. Sabour R. Farrag A.M. Synthesis of new arylazopyrazoles as apoptosis inducers: Candidates to inhibit proliferation of MCF‐7 cells. Arch. Pharm. (Weinheim) 2021 354 1 2000214 10.1002/ardp.202000214 32924168
    [Google Scholar]
  49. Kasiotis K.M. Tzanetou E.N. Haroutounian S.A. Pyrazoles as potential anti-angiogenesis agents: A contemporary overview. Front Chem. 2014 2 SEP 78 10.3389/fchem.2014.00078 25250310
    [Google Scholar]
  50. Wu Z. Yang W. Hou S. Xie D. Yang J. Liu L. Yang S. In vivo antiviral activity and disassembly mechanism of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives against Tobacco mosaic virus. Pestic. Biochem. Physiol. 2021 173 104771 10.1016/j.pestbp.2021.104771 33771249
    [Google Scholar]
  51. Padmini T. Bhikshapathi D. Suresh K. Kulkarni R. Kamal B.R. Novel aminopyrazole tagged hydrazones as anti-tubercular agents: Synthesis and molecular docking studies. Med. Chem. 2021 17 4 344 351 10.2174/1573406416666200514084747 32407282
    [Google Scholar]
  52. Islam M.S. Al-Majid A.M. Sholkamy E.N. Yousuf S. Ayaz M. Nawaz A. Wadood A. Rehman A.U. Verma V.P. Bari A. Haukka M. Soliman S.M. Barakat A. Synthesis, molecular docking and enzyme inhibitory approaches of some new chalcones engrafted pyrazole as potential antialzheimer, antidiabetic and antioxidant agents. J. Mol. Struct. 2022 1269 133843 10.1016/j.molstruc.2022.133843
    [Google Scholar]
  53. Kryštof V. Cankař P. Fryšová I. Slouka J. Kontopidis G. Džubák P. Hajdúch M. Srovnal J. de Azevedo W.F. Orság M. Paprskářová M. Rolčík J. Látr A. Fischer P.M. Strnad M. Effects C. Paprska M. 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J. Med. Chem. 2006 49 22 6500 6509 10.1021/jm0605740 17064068
    [Google Scholar]
  54. Jorda R. Navrátilová J. Hušková Z. Schütznerová E. Cankař P. Strnad M. Kryštof V. Arylazopyrazole AAP1742 inhibits CDKs and induces apoptosis in multiple myeloma cells via Mcl-1 downregulation. Chem. Biol. Drug Des. 2014 84 4 402 408 10.1111/cbdd.12330 24803299
    [Google Scholar]
  55. Lusardi M. Spallarossa A. Brullo C. Amino-pyrazoles in medicinal chemistry: A review. Int. J. Mol. Sci. 2023 24 9 7834 10.3390/ijms24097834
    [Google Scholar]
  56. Ilies M. Banciu M.D. Ilies M.A. Scozzafava A. Caproiu M.T. Supuran C.T. Carbonic anhydrase activators: Design of high affinity isozymes I, II, and IV activators, incorporating tri-/tetrasubstituted-pyridinium-azole moieties. J. Med. Chem. 2002 45 2 504 510 10.1021/jm011031n 11784154
    [Google Scholar]
  57. Maccallini C. Di Matteo M. Vullo D. Ammazzalorso A. Carradori S. De Filippis B. Fantacuzzi M. Giampietro L. Pandolfi A. Supuran C.T. Amoroso R. Indazole, pyrazole, and oxazole derivatives targeting nitric oxide synthases and carbonic anhydrases. ChemMedChem 2016 11 16 1695 1699 10.1002/cmdc.201600204 27377568
    [Google Scholar]
  58. Chiaramonte N. Maach S. Biliotti C. Angeli A. Bartolucci G. Braconi L. Dei S. Teodori E. Supuran C.T. Romanelli M.N. Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine. J. Enzyme Inhib. Med. Chem. 2020 35 1 1003 1010 10.1080/14756366.2020.1749602 32336172
    [Google Scholar]
  59. Khalifah R.G. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem. 1971 246 8 2561 2573 10.1016/S0021‑9258(18)62326‑9 4994926
    [Google Scholar]
  60. Yusuf Z.S. Uysal T.K. Simsek E. Nocentini A. Osman S.M. Supuran C.T. Özensoy Güler Ö. The inhibitory effect of boric acid on hypoxia-regulated tumour-associated carbonic anhydrase IX. J. Enzyme Inhib. Med. Chem. 2022 37 1 1340 1345 10.1080/14756366.2022.2072837 35535546
    [Google Scholar]
  61. Petrou A. Geronikaki A. Terzi E. Guler O.O. Tuccinardi T. Supuran C.T. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with secondary sulfonamides incorporating benzothiazole scaffolds. J. Enzyme Inhib. Med. Chem. 2016 31 6 1306 1311 10.3109/14756366.2015.1128427 26745009
    [Google Scholar]
  62. Küçükbay H. Gönül Z. Küçükbay F.Z. Tekin Z. Angeli A. Bartolucci G. Supuran C.T. Tatlıcı E. Apohan E. Yeşilada Ö. Synthesis of new 7‐amino‐3,4‐dihydroquinolin‐2(1 H)‐one‐peptide derivatives and their carbonic anhydrase enzyme inhibition, antioxidant, and cytotoxic activities. Arch. Pharm. (Weinheim) 2021 354 11 2100122 10.1002/ardp.202100122 34313324
    [Google Scholar]
  63. Mondal U.K. Doroba K. Shabana A.M. Adelberg R. Alam M.R. Supuran C.T. Ilies M.A. PEG linker length strongly affects tumor cell killing by pegylated carbonic anhydrase inhibitors in hypoxic carcinomas expressing carbonic anhydrase IX. Int. J. Mol. Sci. 2021 22 3 1120 10.3390/ijms22031120 33498779
    [Google Scholar]
  64. Eldehna W.M. Abo-Ashour M.F. Berrino E. Vullo D. Ghabbour H.A. Al-Rashood S.T. Hassan G.S. Alkahtani H.M. Almehizia A.A. Alharbi A. Abdel-Aziz H.A. Supuran C.T. SLC-0111 enaminone analogs, 3/4-(3-aryl-3-oxopropenyl) aminobenzenesulfonamides, as novel selective subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform IX. Bioorg. Chem. 2019 83 549 558 10.1016/j.bioorg.2018.11.014 30471577
    [Google Scholar]
  65. Moi D. Vittorio S. Angeli A. Balboni G. Supuran C.T. Onnis V. Investigation on Hydrazonobenzenesulfonamides as Human Carbonic Anhydrase I, II, IX and XII Inhibitors. Molecules 2022 28 1 91 10.3390/molecules28010091 36615285
    [Google Scholar]
  66. Akocak S. Innovative design, synthesis, and in silico evaluation of bis-ureido substituted antipyrine derivatives: Molecular modeling and ADME insights. Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2025 15 1 264 278 10.21597/jist.1591716
    [Google Scholar]
  67. Demir Y. Tokalı F.S. Kalay E. Türkeş C. Tokalı P. Aslan O.N. Şendil K. Beydemir Ş. Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors. Mol. Divers. 2023 27 4 1713 1733 10.1007/s11030‑022‑10526‑1 36103032
    [Google Scholar]
  68. Daina A. Michielin O. Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017 7 42717 10.1038/srep42717
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266373008250723064558
Loading
Exploring the Carbonic Anhydrase Activation Properties of 4-arylazo-3,5-diamino-1H-pyrazoles against hCA I, II, IV, and VII isoenzymes
Bentham Science Publishers ; https://doi.org/10.2174/0115680266373008250723064558
/content/journals/ctmc/10.2174/0115680266373008250723064558
/content/journals/ctmc/10.2174/0115680266373008250723064558
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: Pyrazoles ; Alzheimer’s ; Isoforms ; Brain ; Neurodegenerative ; Carbonic Anhydrase Activator (CAA)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test