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Volume 26, Issue 3
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

Abstract

Background

Sulfonamides are widely used carbonic anhydrase inhibitors (CAIs) in clinical settings, however, their nonspecific inhibition of multiple carbonic anhydrase isoforms can lead to reduced efficacy and side effects. This study aimed to develop sulfanilamide-diazo derivatives incorporating benzoic acid moieties as novel inhibitors of hCA II activity to reduce side effects and enhance selectivity for different CA isozymes.

Methods

We investigated the interaction between these derivatives and the hCA II isozyme various spectroscopic and docking methods.

Results

The kinetic data demonstrates that compound 1 (C1) and compound 2 (C2) share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II a static quenching process, with each compound showing a singular binding site within the enzyme. Thermodynamic evidences highlight the significance of van der Waals interactions and hydrogen bonding in the binding process. The results of molecular docking indicated that both C1 and C2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations.

Conclusion

While C1 and C2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new carbonic anhydrase inhibitors.

© 2025 Bentham Science Publishers
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2024-12-06
2025-04-28

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References

  1. BergJ.M. TymoczkoJ.L. GattoG. StryerL. Biochemistry (eight edition).WH Freeman & Co Ltd2015
     [Google Scholar]
  2. WahiduzZ. DarM.A. HaqueM.A. IdreesD. HassanM.I. IslamA. AhmadF. Characterization of folding intermediates during urea-induced denaturation of human carbonic anhydrase II.Int. J. Biol. Macromol.20179588188710.1016/j.ijbiomac.2016.10.07327789330
     [Google Scholar]
  3. SupuranC.T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators.Nat. Rev. Drug Discov.20087216818110.1038/nrd246718167490
     [Google Scholar]
  4. FatahianB.N. MehrabiM. AdibiH. MehrabiM. KhodarahmiR. Synthesis of 4-sulfamoyl phenyl diazocarboxylic acid derivatives as novel non-classical inhibitors of human carbonic anhydrase II activity: an in vitro study.J. Biomol. Struct. Dyn.202411510.1080/07391102.2024.231077738334282
     [Google Scholar]
  5. InnocentiA. VulloD. ScozzafavaA. SupuranC.T. Carbonic anhydrase inhibitors: Interactions of phenols with the 12 catalytically active mammalian isoforms (CA I–XIV).Bioorg. Med. Chem. Lett.20081851583158710.1016/j.bmcl.2008.01.07718242985
     [Google Scholar]
  6. BeyzaÖ.S.S. Gülçinİ. SupuranC.T. Carbonic anhydrase inhibitors: Inhibition of human erythrocyte isozymes I and II with a series of phenolic acids.Chem. Biol. Drug Des.201075551552010.1111/j.1747‑0285.2010.00965.x20486938
     [Google Scholar]
  7. ŞentürkM. Gülçinİ. BeydemirŞ. KüfrevioğluÖ.İ. SupuranC.T. In Vitro inhibition of human carbonic anhydrase I and II isozymes with natural phenolic compounds.Chem. Biol. Drug Des.201177649449910.1111/j.1747‑0285.2011.01104.x21332948
     [Google Scholar]
  8. BayramE. SenturkM. IrfanK.O. SupuranC.T. In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II.Bioorg. Med. Chem.200816209101910510.1016/j.bmc.2008.09.02818819808
     [Google Scholar]
  9. SinghS. LomelinoC. MbogeM. FrostS. McKennaR. Cancer drug development of carbonic anhydrase inhibitors beyond the active site.Molecules2018235104510.3390/molecules2305104529710858
     [Google Scholar]
  10. ParasuramanS. AnandD.A.V. ArulmoliR. Overviews of biological importance of quercetin: A bioactive flavonoid.Pharmacogn. Rev.20161020848910.4103/0973‑7847.19404428082789
     [Google Scholar]
  11. LangellaE. D’AmbrosioK. D’AscenzioM. CarradoriS. MontiS.M. SupuranC.T. De SimoneG. A combined crystallographic and theoretical study explains the capability of carboxylic acids to adopt multiple binding modes in the active site of carbonic anhydrases.Chemistry20162219710010.1002/chem.20150374826507456
     [Google Scholar]
  12. Abdel-AzizA.A.M. El-AzabA.S. CerusoM. SupuranC.T. Carbonic anhydrase inhibitory activity of sulfonamides and carboxylic acids incorporating cyclic imide scaffolds.Bioorg. Med. Chem. Lett.201424225185518910.1016/j.bmcl.2014.09.07625442309
     [Google Scholar]
  13. SechiM. InnocentiA. PalaN. RogolinoD. CarcelliM. ScozzafavaA. SupuranC.T. Inhibition of α-class cytosolic human carbonic anhydrases I, II, IX and XII, and β-class fungal enzymes by carboxylic acids and their derivatives: New isoform-I selective nanomolar inhibitors.Bioorg. Med. Chem. Lett.201222185801580610.1016/j.bmcl.2012.07.09422901388
     [Google Scholar]
  14. NymanP.O. Purification and properties of carbonic anhydrase from human erythrocytes.Biochim. Biophys. Acta196152111210.1016/0006‑3002(61)90898‑814480808
     [Google Scholar]
  15. LowryO. RosebroughN. FarrA.L. RandallR. Protein measurement with the Folin phenol reagent.J. Biol. Chem.1951193126527510.1016/S0021‑9258(19)52451‑614907713
     [Google Scholar]
  16. PockerY. StoneJ.T. The catalytic versatility of erythrocyte carbonic anhydrase. 3. Kinetic studies of the enzyme-catalyzed hydrolysis of p-nitrophenyl acetate.Biochemistry19676366867810.1021/bi00855a0054960944
     [Google Scholar]
  17. SheehanD. Physical biochemistry: principles and applications.John Wiley & Sons2013
     [Google Scholar]
  18. FengX.Z. LinZ. YangL.J. WangC. BaiC. Investigation of the interaction between acridine orange and bovine serum albumin.Talanta19984751223122910.1016/S0039‑9140(98)00198‑218967427
     [Google Scholar]
  19. HouH.N. QiZ.D. OuYangY.W. LiaoF.L. ZhangY. LiuY. Studies on interaction between Vitamin B12 and human serum albumin.J. Pharm. Biomed. Anal.200847113413910.1016/j.jpba.2007.12.02918261869
     [Google Scholar]
  20. MehrabiM. GhobadiS. KhodarahmiR. Spectroscopic study on the interaction of celecoxib with human carbonic anhydrase II: Thermodynamic characterization of the binding process.J. Photochem. Photobiol. B200997316116810.1016/j.jphotobiol.2009.09.00519879770
     [Google Scholar]
  21. CoiA. BianucciA.M. BonomiF. RasmussenP. MuraG.M. GanaduM.L. Structural perturbation of αB-crystallin by zinc and temperature related to its chaperone-like activity.Int. J. Biol. Macromol.200842322923410.1016/j.ijbiomac.2007.10.01218048095
     [Google Scholar]
  22. MöllerM. DenicolaA. Study of protein‐ligand binding by fluorescence.Biochem. Mol. Biol. Educ.200230530931210.1002/bmb.2002.494030050089
     [Google Scholar]
  23. RahmanM.H. MaruyamaT. OkadaT. YamasakiK. OtagiriM. Study of interaction of carprofen and its enantiomers with human serum albumin—I.Biochem. Pharmacol.199346101721173110.1016/0006‑2952(93)90576‑I7504487
     [Google Scholar]
  24. JobP. Formation and stability of inorganic complexes in solution.Ann. Chim.1928910113134
     [Google Scholar]
  25. WardL.D. Measurement of ligand binding to proteins by fluorescence spectroscopy.Meth. Enzymol.198511740041410.1016/S0076‑6879(85)17024‑2
     [Google Scholar]
  26. MehrabiM. KhodarahmiR. ShahlaeiM. Critical effects on binding of epidermal growth factor produced by amino acid substitutions.J. Biomol. Struct. Dyn.20173551085110110.1080/07391102.2016.117179927212100
     [Google Scholar]
  27. RasouliH. MehrabiM. ArabS.S. KhodarahmiR. Are Pro 8/Pro 18 really critical for functional dynamic behavior of human endostatin N-terminal peptide? A comparative molecular dynamics study.J. Indian Chem. Soc.20171420232039
     [Google Scholar]
  28. MiaoM. JiangB. JiangH. ZhangT. LiX. Interaction mechanism between green tea extract and human α-amylase for reducing starch digestion.Food Chem.2015186202510.1016/j.foodchem.2015.02.04925976786
     [Google Scholar]
  29. MehrabiM. EsmaeiliS. EzatiM. AbassiM. RasouliH. NazariD. AdibiH. KhodarahmiR. Antioxidant and glycohydrolase inhibitory behavior of curcumin-based compounds: Synthesis and evaluation of anti-diabetic properties in vitro.Bioorg. Chem.202111010472010.1016/j.bioorg.2021.10472033662896
     [Google Scholar]
  30. CartaF. SupuranC.T. ScozzafavaA. Sulfonamides and their isosters as carbonic anhydrase inhibitors.Future Med. Chem.20146101149116510.4155/fmc.14.6825078135
     [Google Scholar]
  31. LomelinoC. SupuranC. McKennaR. Non-classical inhibition of carbonic anhydrase.Int. J. Mol. Sci.2016177115010.3390/ijms1707115027438828
     [Google Scholar]
  32. FadilahF. ArsiantiA. YanuarA. AndrajatiR. IndahP.R. HernawatiP.E. Structure activity relationship analysis of antioxidant activity of simple benzene carboxylic acids group based on multiple linear regression.Orient. J. Chem.20183452656266010.13005/ojc/340558
     [Google Scholar]
  33. BozdagM. FerraroniM. NutiE. VulloD. RosselloA. CartaF. ScozzafavaA. SupuranC.T. Combining the tail and the ring approaches for obtaining potent and isoform-selective carbonic anhydrase inhibitors: Solution and X-ray crystallographic studies.Bioorg. Med. Chem.201422133434010.1016/j.bmc.2013.11.01624300919
     [Google Scholar]
  34. MoghoufeiL. MehrabiM. AdibiH. KhodarahmiR. Synthesis of 4-hydroxy-L-proline derivatives as new non-classical inhibitors of human carbonic anhydrase II activity: An in vitro study.J. Biomol. Struct. Dyn.202211136166619
     [Google Scholar]
  35. EsmaeiliS. Ashrafi-KooshkM.R. AdibiH. KhodarahmiR. Captopril/enalapril inhibit promiscuous esterase activity of carbonic anhydrase at micromolar concentrations: An in vitro study.Chem. Biol. Interact.2017265243510.1016/j.cbi.2017.01.01428126276
     [Google Scholar]
  36. AryaA. KumarA.J.B. EducationM.B. Inconsistencies in some common terms and notations in enzymology: Textbook examples and suggestions.Biochem. Mol. Biol. Educ.201947214014410.1002/bmb.21204
     [Google Scholar]
  37. PalmerT. BonnerP.L. Enzymes: biochemistry, biotechnology, clinical chemistry.Elsevier200710.1533/9780857099921
     [Google Scholar]
  38. RanjbarS. GhobadiS. KhodarahmiR. Spectroscopic characterization of furosemide binding to human carbonic anhydrase II. Int. J. Biol. Macromol.201250491091710.1016/j.ijbiomac.2012.02.005.
     [Google Scholar]
  39. FreifelderD. Physical biochemistry: applications to biochemistry and molecular biology.Macmillan1982
     [Google Scholar]
  40. HeW. LiY. XueC. HuZ. ChenX. ShengF.J.B. Effect of Chinese medicine alpinetin on the structure of human serum albumin.Bioorg. Med. Chem.20051351837184510.1016/j.bmc.2004.11.038
     [Google Scholar]
  41. ZhaoX. MengX. RagauskasA.J. LaiC. LingZ. HuangC. YongQ. Unlocking the secret of lignin-enzyme interactions: Recent advances in developing state-of-the-art analytical techniques.Biotechnol. Adv.20225410783010.1016/j.biotechadv.2021.10783034480987
     [Google Scholar]
  42. TrangT.T. PhamT.T.H. DangN.V. NgaP.T. LinhM.V. VuX.H. Revealing the high efficiency of fluorescence quenching of rhodamine B by triangular silver nanodisks due to the inner filter effect mechanism.RSC Advances202414149538954610.1039/D4RA00575A38516156
     [Google Scholar]
  43. KhateriS. MehrabiM. KhodarahmiR. Inhibitory effects of quercetin and resveratrol and their sulfonamide derivatives on the carbonic anhydrase activity: spectroscopic studies of the binding process.Chem. Zvesti202478115116310.1007/s11696‑023‑03048‑z
     [Google Scholar]
  44. AssaranD.R. ShareghiB. AsoodehA. ChamaniJ. Multi-spectroscopic and molecular modeling studies of interaction between two different angiotensin I converting enzyme inhibitory peptides from gluten hydrolysate and human serum albumin.J. Biomol. Struct. Dyn.201735163648366210.1080/07391102.2016.126489227897084
     [Google Scholar]
  45. BagliniE. RavichandranR. BerrinoE. SalernoS. BarresiE. MariniA.M. VivianoM. CastellanoS. Da SettimoF. SupuranC.T. CosconatiS. TalianiS. Tetrahydroquinazole-based secondary sulphonamides as carbonic anhydrase inhibitors: synthesis, biological evaluation against isoforms I, II, IV, and IX, and computational studies.J. Enzyme Inhib. Med. Chem.20213611874188310.1080/14756366.2021.195691334340614
     [Google Scholar]
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Discovery of Sulfanilamide-diazo Derivatives Incorporating Benzoic Acid Moieties as Novel Inhibitors of Human Carbonic Anhydrase II Activity
Curr. Protein Pept. Sci. 26, 226 (2025); https://doi.org/10.2174/0113892037332139241008054602
/content/journals/cpps/10.2174/0113892037332139241008054602
/content/journals/cpps/10.2174/0113892037332139241008054602
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  • Article Type:     Research Article
Keyword(s): Carbonic anhydrase inhibitors; carboxylic acid/sulfonamide compounds; docking; fluorescence; quenching; synthesis

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