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Acetylphenyl-substituted imidazolium salts: synthesis, characterization, in silico studies and inhibitory properties against some metabolic enzymes

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Abstract

Herein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (1H NMR, 13C NMR, 19F NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds’ the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with Ki values in the range of 8.30 ± 1.71 to 120.77 ± 8.61 nM for AChE, 16.97 ± 2.04 to 84.45 ± 13.78 nM for hCA I, and 14.09 ± 2.99 to 69.33 ± 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.

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References

  1. Wang MP, Chiu CC, Lu TJ, Lee DS (2018) Indolylbenzimidazole-based ligands catalyze the coupling of arylboronic acids with aryl halides. Appl Organomet Chem 32:e4348

    Article  Google Scholar 

  2. Nguyen VH, Dang TT, Nguyen HH, Huynh HV (2020) Platinium(II) 1,2,4-triazolin-5-ylidene complexes: stereoelectronic influences on their catalytic activity in hydroelementation reactions. Organometallics 39:2309–2319

    Article  CAS  Google Scholar 

  3. Herrmann WA, Goo βen LJ, Spiegler M, (1997) Functionalized imidazoline-2-ylidene complexes of rhodium and palladium. J Organomet Chem 547:357–366

    Article  CAS  Google Scholar 

  4. Marion N, Nolan SP (2008) N-Heterocyclic carbenes in gold catalysis. Chem Soc Rev 37:1776–1782

    Article  CAS  PubMed  Google Scholar 

  5. Ung G, Soleilhavoup M, Bertrand G (2013) Gold(III)- versus gold(i)-induced cyclization: synthesis of six-membered mesoionic carbene and acyclic (aryl)(heteroaryl) carbene complexes. Angew Chem Int Ed Engl 52:758–761

    Article  CAS  PubMed  Google Scholar 

  6. El-Gohary NS, Shaaban MI (2017) Synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents. Eur J Med Chem 131:255–262

    Article  CAS  PubMed  Google Scholar 

  7. Albayrak S, Gök Y, Sari Y, Taskın Tok T, Aktaş A (2021) Benzimidazolium salts bearing 2-methyl-1,4-benzodioxane group: synthesis, characterization, computational studies, in vitro antioxidant and antimicrobial activity. Biointerface Res Appl Chem 11:13333–13346

    Article  CAS  Google Scholar 

  8. Malinowska M, Sawicka D, Niemirowicz-Laskowska K, Wielgat P, Car H, Hauschild T, Hryniewicka A (2021) Steroid-functionalized imidazolium salts with an extended spectrum of antifungal and antibacterial activity. Int J Mol Sci 22:12180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Song XQ, Vig BS, Lorenzi PL, Drach JC, Townsend LB, Amidon GL (2005) Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole as potential substrates of hpept1 transporter. J Med Chem 48:1274–1277

    Article  CAS  PubMed  Google Scholar 

  10. Bukhari SNA, Lauro G, Jantan I, Chee CF, Amjad MW, Bifulco G, Sher H, Addullah I, Abd Rahman N (2016) Anti-inflammatory trends of new benzimidazole derivatives. Future Med Chem 8:1953–1967

    Article  CAS  PubMed  Google Scholar 

  11. Fan QW, Zhong QD, Yan H (2017) Synthesis, antitumor activity, and docking study of 1,3-disubstituted imidazolium derivatives. Russ J Gen Chem 87:3023–3028

    Article  CAS  Google Scholar 

  12. Aher SB, Muskawar PN, Thenmozhi K, Bhagat PR (2014) Recent developments of metal n-heterocyclic carbenes as anticancer agents. Eur J Med Chem 81:408–419

    Article  CAS  PubMed  Google Scholar 

  13. Yadav G, Ganguly S (2015) Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review. Eur J Med Chem 97:419–443

    Article  CAS  PubMed  Google Scholar 

  14. Kotovskaya SK, Zhumabaeva GA, Perova NM, Baskakova ZM, Charushin VN, Chupakhin ON, Belanov EF, Bormotov NI, Balakhnin SM, Serova OA (2007) Synthesis and antiviral activity of fluorinated 3-phenyl-1,2,4-benzotriazines. Pharm Chem J 41(2):62–68

    Article  CAS  Google Scholar 

  15. Wu L, Wang X (2014) One-pot synthesis of 1-aryl-1H,3H-thiazolo[3,4-a]benzimidazoles using magnetite-linked sulfonic acid as catalyst. Phosphorus Sulfur Silicon Relat Elem 189:1851–1857

    Article  CAS  Google Scholar 

  16. Abdel-Hafez AA (2007) Benzimidazole condensed ring systems: New synthesis and antineoplastic activity of substituted 3,4-dihydro- and 1,2,3,4-tetrahydro-benzo [4,5]imidazo[1,2-a]pyrinnidine derivatives. Arch Pharm Res 30:678–684

    Article  CAS  Google Scholar 

  17. Kühl O, Palm G (2010) Imidazolium salts from amino acids—a new route to chiral zwitterionic carbene precursors. Tetrahedron Asymmetry 21:393–397

    Article  Google Scholar 

  18. Yang S, Zhang Q, Hu Y, Ding G, Wang J, Huo S, Zhang B, Cheng J (2018) Synthesis of s-triazine based tri-imidazole derivatives and their application as thermal latent curing agents for epoxy resin. Mater Lett 216:127–130

    Article  CAS  Google Scholar 

  19. Padvi SA, Dalal DS (2020) Task-specific ionic liquids as a green catalysts and solvents for organic synthesis. Curr Green Chem 7:105–119

    Article  CAS  Google Scholar 

  20. Bando T, Hiroshi S (2006) Synthesis and biological properties of sequence-specific DNA-alkylating pyrrole-imidazole polyamides. Acc Chem Res 39:935–944

    Article  CAS  PubMed  Google Scholar 

  21. Bredas JL, Poskin MP, Delhalle J, Andre JM, Chojnacki H (1984) Electronic structure of hydrogen-bonded imidazole chains. Influence of the proton position. J Phys Chem 88:5882–5887

    Article  CAS  Google Scholar 

  22. Ganapathi P, Ganesan K, Vijaykanth N, Arunagirinathan N (2016) Anti-bacterial screening of water soluble carbonyl diimidazolium salts and its derivatives. J Mol Liq 219:180–185

    Article  CAS  Google Scholar 

  23. Anderson EB, Long TE (2010) Imidazole- and imidazolium-containing polymers for biology and material science applications. Polymer 51:2447–2454

    Article  CAS  Google Scholar 

  24. Grygorenko OO, Volochnyuk DM, Ryabukhin SV, Judd DB (2020) The symbiotic relationship between drug discovery and organic chemistry. Chem Eur J 26:1196–1237

    Article  CAS  PubMed  Google Scholar 

  25. Meanwell NA (2011) Improving drug candidates by design: A focus on physicochemical properties as a means of improving compound disposition and safety. Chem Res Toxicol 24:1420–1456

    Article  CAS  PubMed  Google Scholar 

  26. Begue JP, Bonnet-Delpon D (2008) Bioorganic and Medicinal Chemistry of Fluorine. John Wiley & Sons, Hoboken, p 365

    Book  Google Scholar 

  27. Meanwell NA (2018) Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design. J Med Chem 61:5822–5880

    Article  CAS  PubMed  Google Scholar 

  28. Han J, Remete AM, Dobson LS, Kiss L, Izawa K, Moriwaki H, Soloshonok VA, O’Hagan D (2020) Next generation organofluorine containing blockbuster drugs. J Fluorine Chem 239:109639

    Article  CAS  Google Scholar 

  29. Hanson JR (2001) Functional group chemistry. Royal Society of Chemistry, Cambridge, Eng

    Book  Google Scholar 

  30. Lehninger AL, Nelson DL, Cox MM, Cox MM (2005) Lehninger principles of biochemistry. Macmillan

    Google Scholar 

  31. Gülçin İ (2006) Antioxidant and antiradical activities of L-Carnitine. Life Sci 78:803–811

    Article  PubMed  Google Scholar 

  32. Gülçin İ (2010) Antioxidant properties of resveratrol: A structure-activity insight. Innov Food Sci Emerg Technol 11:210–218

    Article  Google Scholar 

  33. Bilginer S, Gul HI, Anil B, Demir Y, Gulcin I (2021) Synthesis and in silico studies of triazene-substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors. Arch Pharm 354:2000243

    Article  CAS  Google Scholar 

  34. Bilginer S, Anil B, Koca M, Demir Y, Gülçin İ (2021) Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl) phenyl] acryloyl}-2 (3H)-benzoxazolones. Turk J Chem 45:805–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gümüş M, Babacan ŞN, Demir Y, Sert Y, Koca İ, Gülçin İ (2022) Discovery of sulfadrug-pyrrole conjugates as carbonic anhydrase and acetylcholinesterase inhibitors. Arch Pharm 355:e2100242

    Article  Google Scholar 

  36. Mahmudov I, Demir Y, Sert Y, Abdullayev Y, Sujayev A, Alwasel SH, Gulcin I (2022) Synthesis and inhibition profiles of N-benzyl- and N-allyl aniline derivatives against carbonic anhydrase and acetylcholinesterase – A molecular docking study. Arab J Chem 15:103645

    Article  CAS  Google Scholar 

  37. Aydın BO, Anil D, Demir Y (2021) Synthesis of N-alkylated pyrazolo[3,4-d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties. Arch Pharm 354:2000330

    Article  Google Scholar 

  38. Kaya Y, Erçağ A, Zorlu Y, Demir Y, Gülçin İ (2022) New Pd(II) complexes of the bisthiocarbohydrazones derived from isatin and disubstituted salicylaldehydes: Synthesis, characterization, crystal structures and inhibitory properties against some metabolic enzymes. J Biol Inorg Chem 27:271–281

    Article  CAS  PubMed  Google Scholar 

  39. Ozbey F, Taslimi P, Gulcin İ, Maraş A, Goksu S, Supuran CT (2016) Synthesis, acetylcholinesterase, butyrilcholinesterase, carbonic anhydrase inhibitory and metal chelating properties of some novel diaryl ether. J Enzyme Inhib Med Chem 31:79–85

    Article  CAS  PubMed  Google Scholar 

  40. Supuran CT (2021) Emerging role of carbonic anhydrase inhibitors. Clin Sci 135:1233–1249

    Article  CAS  Google Scholar 

  41. Turkan F, Cetin A, Taslimi P, Karaman M, Gülçin İ (2019) Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg Chem 86:420–427

    Article  CAS  PubMed  Google Scholar 

  42. Nar M, Çetinkaya Y, Gülçin İ, Menzek A (2013) (3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives as carbonic anhydrase isoenzymes inhibitors. J Enzyme Inhib Med Chem 28:402–406

    Article  PubMed  Google Scholar 

  43. Küçük M, Gülçin İ (2016) Purification and characterization of carbonic anhydrase enzyme from black sea trout (Salmo trutta Labrax Coruhensis) kidney and inhibition effects of some metal ions on the enzyme activity. Environ Toxicol Pharmacol 44:134–139

    Article  PubMed  Google Scholar 

  44. Hisar O, Beydemir Ş, Gülçin İ, Küfrevioğlu Öİ, Supuran CT (2005) Effect of low molecular weight plasma inhibitors of rainbow trout (Oncorhyncytes mykiss) on human erythrocytes carbonic anhydrase-II isozyme activity in vitro and rat erythrocytes in vivo. J Enzyme Inhib Med Chem 20:35–39

    Article  CAS  PubMed  Google Scholar 

  45. Tugrak M, Gul HI, Demir Y, Levent S, Gulcin I (2021) Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone-based benzenesulfonamides. Arch Pharm 354:2000375

    Article  CAS  Google Scholar 

  46. Yamali C, Gul HI, Cakir T, Demir Y, Gulcin I (2020) Aminoalkylated phenolic chalcones: Investigation of biological effects on acetylcholinesterase and carbonic anhydrase i and ii as potential lead enzyme inhibitors. Lett Drug Des Discovery 17:1283–1292

    Article  CAS  Google Scholar 

  47. Askin S, Tahtaci H, Türkeş C, Demir Y, Ece A, Akalın Çiftçi G, Beydemir Ş (2021) Design, synthesis, characterization, in vitro and in silico evaluation of novel imidazo[2,1-b][1,3,4]thiadiazoles as highly potent acetylcholinesterase and non-classical carbonic anhydrase inhibitors. Bioorg Chem 113:105009

    Article  CAS  PubMed  Google Scholar 

  48. Kalaycı M, Türkeş C, Arslan M, Demir Y, Beydemir Ş (2021) Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors. Arch Pharm 354:e2000282

    Article  Google Scholar 

  49. Ozgeris B, Göksu S, Köse Polat L, Gülçin İ, Salmas RE, Durdagi S, Tümer F, Supuran CT (2016) Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds. Bioorg Med Chem 24:2318–2329

    Article  CAS  PubMed  Google Scholar 

  50. Garibov E, Taslimi P, Sujayev A, Bingöl Z, Çetinkaya S, Gulcin İ, Beydemir S, Farzaliyev V, Alwasel SH, Supuran CT (2016) Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. J Enzyme Inhibition Med Chem 31:1–9

    Article  CAS  Google Scholar 

  51. Burmaoğlu S, Yılmaz AO, Polat MF, Kaya R, Gülçin İ, Algül Ö (2019) Synthesis and biological evaluation of novel tris-chalcones as potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase inhibitors. Bioorg Chem 85:191–197

    Article  PubMed  Google Scholar 

  52. Erdemir F, Barut Celepci D, Aktaş A, Gök Y, Kaya R, Taslimi P, Demir Y, Gülçin İ (2019) Novel 2-aminopyridine liganded Pd(II) N-heterocyclic carbene complexes: synthesis, characterization, crystal structure and bioactivity properties. Bioorg Chem 91:103134

    Article  CAS  PubMed  Google Scholar 

  53. Bayrak Ç, Taslimi P, Kahraman HS, Gülçin İ, Menzek A (2019) The first synthesis, carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products. Bioorg Chem 85:128–139

    Article  CAS  PubMed  Google Scholar 

  54. Huseynova M, Taslimi P, Medjidov A, Farzaliyev V, Aliyeva M, Gondolova G, Şahin O, Yalçın B, Sujayev A, Orman EB, Özkaya AR, Gülçin İ (2018) Synthesis, characterization, crystal structure, electrochemical studies and biological evaluation of metal complexes with thiosemicarbazone of glyoxylic acid. Polyhedron 155:25–33

    Article  CAS  Google Scholar 

  55. Çetin Çakmak K, Gülçin İ (2019) Anticholinergic and antioxidant activities of usnic acid-An activity-structure insight. Toxicol Rep 6:1273–1280

    Article  PubMed  PubMed Central  Google Scholar 

  56. Sever B, Türkeş C, Altıntop MD, Demir Y, Akalın Çiftçi G, Beydemir Ş (2021) Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds. Arch Pharm 354:e2100294

    Article  Google Scholar 

  57. Şahin İ, Bingöl Z, Onur S, Güngör SA, Köse M, Gülçin İ, Tümer F (2022) Enzyme inhibition properties and molecular docking studies of 4-sulfonate containing aryl α-hydroxyphosphonates based hybrid molecules. Chem Biodivers 19:e202100787

    Article  PubMed  Google Scholar 

  58. Gülçin İ, Scozzafava A, Supuran CT, Akıncıoğlu H, Koksal Z, Turkan F, Alwasel S (2016) The effect of caffeic acid phenethyl ester (CAPE) metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione s-transferase, lactoperoxidase and carbonic anhydrase isoenzymes I, II, IX and XII. J Enzyme Inhib Med Chem 31:1095–1101

    Article  PubMed  Google Scholar 

  59. Taslimi P, Caglayan C, Gulçin İ (2017) The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes: an antidiabetic, anticholinergic, and antiepileptic study. J Biochem Mol Toxicol 31:e21995

    Article  Google Scholar 

  60. Takım K, Yigin A, Koyuncu İ, Kaya R, Gulçin İ (2021) Anticancer, anticholinesterase and antidiabetic activities of Tunceli garlic (Allium tuncelianum) - Determining its phytochemical content by LC-MS/MS analysis. J Food Meas Characterization 15:3323–3335

    Article  Google Scholar 

  61. Akıncıoğlu A, Göksu S, Naderi A, Akıncıoğlu H, Kılınç N, Gülçin İ (2021) Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones. Comput Biol Chem 94:107565

    Article  PubMed  Google Scholar 

  62. Riaz MT, Yaqup M, Shafiq Z, Ashraf Z, Khalid M, Taslimi P, Taş R, Tuzun B, Gulçin İ (2021) Synthesis, biological activity and docking calculations of bis-naphthoquinone derivatives from lawsone. Bioorg Chem 114:105069

    Article  CAS  PubMed  Google Scholar 

  63. Kızıltaş H, Bingol Z, Goren AC, Alwasel SH, Gülçin İ (2021) Anticholinergic, antidiabetic and antioxidant activities of Ferula orientalis L.-Analysis of its polyphenol contents by LC-HRMS. Rec Nat Prod 15:513–528

    Article  Google Scholar 

  64. Atmaca U, Alp C, Akıncıoğlu H, Karaman HS, Gulçin İ, Çelik M (2021) Novel hypervalent iodine catalyzed synthesis of α-sulfonoxy ketones: Biological activity and molecular docking studies. J Mol Struct 1239:130492

    Article  CAS  Google Scholar 

  65. Karataş MO, Uslu H, Alıcı B, Gökçe B, Gencer N, Arslan O, Arslan NB, Özdemir N (2016) Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies. Bioorg Med Chem 24:1392–1401

    Article  PubMed  Google Scholar 

  66. Hamide M, Gök Y, Demir Y, Yakalı G, Taskin Tok T, Aktaş A, Sevinçek R, Güzel B, Gülçin İ (2022) Pentafluorobenzyl-substituted Benzimidazolium salts: Synthesis, characterization, crystal structures, computational studies and inhibitory properties of some metabolic enzymes. J Mol Struct 1265:133266

    Article  CAS  Google Scholar 

  67. Tezcan B, Gök Y, Sevinçek R, Taslami P, Taskin-Tok T, Aktaş A, Güzel B, Aygün M, Gülçin İ (2022) Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α-glycosidase. J Biochem Mol Toxicol 36:e23001

    Article  CAS  PubMed  Google Scholar 

  68. Kazancı A, Gök Y, Kaya R, Aktaş A, Taslimi P, Gülçin İ (2021) Synthesis, characterization and bioactivities of dative donor ligand N-heterocyclic carbene (NHC) precursors and their Ag(I)NHC coordination compounds. Polyhedron 193:114866

    Article  Google Scholar 

  69. Aktaş A, Noma SAA, Barut Celepci D, Erdemir F, Gök Y, Ateş B (2019) New 2-hydroxyethyl substituted N-Heterocyclic carbene precursors: Synthesis, characterization, crystal structure and inhibitory properties against carbonic anhydrase and xanthine oxidase. J Mol Struct 1184:487–494

    Article  Google Scholar 

  70. Dolbier WR (2009) Guide to Fluorine NMR for Orgonic Chemists. Wilev, Hoboken, p 79

    Book  Google Scholar 

  71. Burmaoglu S, Yilmaz AO, Polat MF, Kaya R, Gulcin İ, Algul O (2021) Synthesis of novel tris-chalcones and determination of their inhibition profiles against some metabolic enzymes. Arch Physiol Biochem 127:153–161

    Article  CAS  PubMed  Google Scholar 

  72. Tokalı FS, Taslimi P, Demircioğlu İH, Karaman M, Gültekin MS, Şendil K, Gülçin İ (2021) Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives. Arch Pharm 354:e2000455

    Article  Google Scholar 

  73. Erdoğan M, Polat Köse L, Eşsiz S, Gülçin İ (2021) Synthesis and biological evaluation of some 1-naphthol derivatives as antioxidants, acetylcholinesterase, and carbonic anhydrase inhibitors. Arch Pharm 354:e2100113

    Article  Google Scholar 

  74. Güney M, Coşkun A, Topal F, Daştan A, Gülçin İ, Supuran CT (2014) Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives. Bioorg Med Chem 22:3537–3543

    Article  PubMed  Google Scholar 

  75. Krymov SK, Scherbakov AM, Salnikova DI, Sorokin DV, Dezhenkova LG, Ivanov IV, Vullo D, De Luca V, Capasso C, Supuran CT, Shchekotikhin AE (2022) Synthesis, biological evaluation, and in silico studies of potential activators of apoptosis and carbonic anhydrase inhibitors on isatin-5-sulfonamide scaffold. Eur J Med Chem 228:113997

    Article  CAS  PubMed  Google Scholar 

  76. Supuran CT (2008) Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 7:168–181

    Article  CAS  PubMed  Google Scholar 

  77. Bekku S, Mochizuki H, Yamamoto T, Ueno H, Takayama E, Tadakuma T (2000) Expression of carbonic anhydrase I or II and correlation to clinical aspects of colorectal cancer. Hepatogastroenterology 47:998–1001

    CAS  PubMed  Google Scholar 

  78. Scozzafava A, Kalın P, Supuran CT, Gülçin İ, Alwasel S (2015) The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII). J Enzyme Inhib Med Chem 30:941–946

    Article  CAS  PubMed  Google Scholar 

  79. Ozmen Ozgün D, Gül Hİ, Yamali C, Sakagami H, Gulçin İ, Sukuroglu M, Supuran CT (2019) Synthesis and bioactivities of pyrazoline benzensulfonamides as carbonic anhydrase and acetylcholinesterase inhibitors with low cytotoxicity. Bioorg Chem 84:511–517

    Article  PubMed  Google Scholar 

  80. Bal S, Kaya R, Gök Y, Taslimi P, Aktaş A, Karaman M, Gülçin İ (2020) Novel 2-methylimidazolium salts: Synthesis, characterization, molecular docking, and carbonic anhydrase and acetylcholinesterase inhibitory properties. Bioorg Chem 94:103468

    Article  CAS  PubMed  Google Scholar 

  81. Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  82. Koçyiğit UM, Budak Y, Gürdere MB, Ertürk F, Yencilek B, Taslimi P, Gulçin İ, Ceylan M (2018) Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles. Arch Physiol Biochem 124:61–68

    Article  PubMed  Google Scholar 

  83. Küçükoğlu K, Gül Hİ, Taslimi P, Gülçin İ, Supuran CT (2019) Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes. Bioorg Chem 86:316–321

    Article  PubMed  Google Scholar 

  84. Taslimi P, Türkan F, Güngördü Solğun D, Aras A, Erden Y, Celebioglu HU, Tuzun B, Ağırtaş MS, Günay S, Gulcin I (2022) Metal contained Phthalocyanines with 3,4-Dimethoxyphenethoxy substituents: their anticancer, antibacterial activities and their inhibitory effects on some metabolic enzymes with molecular docking studies. J Biomol Struct Dyn 40:2991–3002

    Article  CAS  PubMed  Google Scholar 

  85. Akıncıoğlu A, Topal M, Gülçin İ, Göksu S (2014) Novel sulfamides and sulfonamides incorporating tetralin scaffold as carbonic anhydrase and acetylcholine esterase inhibitors. Arch Pharm 347:68–76

    Article  Google Scholar 

  86. Huseynova A, Kaya R, Taslimi P, Farzaliyev V, Mammadyarova X, Sujayev A, Tüzün B, Kocyigit UM, Alwasel S, Gulçin İ (2022) Design, synthesis, characterization, biological evaluation, and molecular docking studies of novel 1,2-aminopropanthiols substituted derivatives as selective carbonic anhydrase, acetylcholinesterase and α-glycosidase enzymes inhibitors. J Biomol Struct Dyn 40:236–248

    Article  CAS  PubMed  Google Scholar 

  87. Taslimi P, Gülçin İ, Öztaşkın N, Çetinkaya Y, Göksu S, Alwasel SH, Supuran CT (2016) The effects of some bromophenol derivatives on human carbonic anhydrase isoenzymes. J Enzyme Inhib Med Chem 31:603–607

    Article  CAS  PubMed  Google Scholar 

  88. Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  89. Köksal E, Gülçin İ (2008) Purification and characterization of peroxidase from cauliflower (Brassica oleracea L.) buds. Protein Peptide Lett 15:320–326

    Article  Google Scholar 

  90. Turan B, Sendil K, Sengul E, Gultekin MS, Taslimi P, Gulcin İ, Supuran CT (2016) The synthesis of some β-lactams and investigation of their metal chelating activity, carbonic anhydrase and achetylcholinesterase inhibition profiles. J Enzyme Inhib Med Chem 31:79–88

    Article  CAS  PubMed  Google Scholar 

  91. Gul HI, Mete E, Taslimi P, Gulcin I, Supuran CT (2017) Synthesis, carbonic anhydrase I and II inhibition studies of the 1,3,5-trisubstituted-pyrazolines. J Enzyme Inhib Med Chem 32:189–192

    Article  CAS  PubMed  Google Scholar 

  92. Verpoorte JA, Mehta S, Edsall JT (1967) Esterase activities of human carbonic anhydrases B and C. J Biol Chem 242:4221–4229

    Article  CAS  PubMed  Google Scholar 

  93. Sujayev A, Garibov E, Taslimi P, Gülçin İ, Gojayeva S, Farzaliyev V, Alwasel SH, Supuran CT (2016) Synthesis of some tetrahydropyrimidine-5-carboxylates, determination of their metal chelating effects and inhibition profiles against acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase. J Enzyme Inhib Med Chem 31:1531–1539

    Article  CAS  PubMed  Google Scholar 

  94. Caglayan C, Taslimi P, Türk C, Gulcin İ, Kandemir FM, Demir Y, Beydemir Ş (2020) Inhibition effects of some pesticides and heavy metals on carbonic anhydrase enzyme activity purified from horse mackerel (Trachurus trachurus) gill tissues. Environ Sci Pollut Res Int 27:10607–10616

    Article  CAS  PubMed  Google Scholar 

  95. Artunc T, Menzek A, Taslimi P, Gulcin I, Kazaz C, Sahin E (2020) Synthesis and antioxidant activities of phenol derivatives from 1,6-bis(dimethoxyphenyl)hexane-1,6-dione. Bioorg Chem 100:103884

    Article  CAS  PubMed  Google Scholar 

  96. Gulçin I, Alwasel SH (2022) Metal ions, metal chelators and metal chelating assay as antioxidant method. Processes 10(1):132

    Article  Google Scholar 

  97. Spassov VZ, Yan L (2013) Accelrys Software Inc., discovery studio modeling environment, release 4.0. Proteins Struct Funct Bioinforma 81:704–714

    Article  CAS  Google Scholar 

  98. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM: A program for macromolecular energy minimization and dynamics calculations. J Comp Chem 4:187–217

    Article  CAS  Google Scholar 

  99. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, et. al (2009) Wallingford CT Gaussian 09 Revision E.01.

  100. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS et al (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 23:3–25

    Article  CAS  Google Scholar 

  102. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623

    Article  CAS  PubMed  Google Scholar 

  103. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3–25

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the İnönü University Faculty of Science Department of Chemistry for the spectroscopy data and characterization of compounds. The authors also thank Esin Akı Yalcin and the research group for technical assistance. This study was financially supported by Inonu University Research Fund (Project Code: FBG‐2021-2525 and FOA-2021-2320).

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Arts and Science, Inönü University, 44280, Malatya, Turkey

    Özlem Demirci & Yetkin Gök

  2. Department of Chemistry, Faculty of Arts and Science, Cukurova University, 01330, Adana, Turkey

    Burcu Tezcan & Bilgehan Güzel

  3. Nihat Delibalta Göle Vocational High School, Ardahan University, 75700, Ardahan, Turkey

    Yeliz Demir

  4. Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, 27310, Gaziantep, Turkey

    Tugba Taskin-Tok

  5. Department of Bioinformatics and Computational Biology, Institute of Health Sciences, Gaziantep University, 27310, Gaziantep, Turkey

    Tugba Taskin-Tok

  6. Organic and Organometallic Chemistry Research Laboratory, Department of Chemistry, Faculty of Arts and Science, Inönü University, 44280, Malatya, Turkey

    Yetkin Gök

  7. Vocational School of Health Service, Inonu University, 44280, Malatya,, Turkey

    Aydın Aktaş

  8. Faculty of Science, Department of Chemistry, Atatürk University, 25240, Erzurum, Turkey

    İlhami Gülçin

Authors
  1. Özlem Demirci
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  2. Burcu Tezcan
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  3. Yeliz Demir
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  4. Tugba Taskin-Tok
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  5. Yetkin Gök
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  6. Aydın Aktaş
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  7. Bilgehan Güzel
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  8. İlhami Gülçin
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Contributions

İlhami Gülçin: Conceptualization and methodology. Özlem Demirci and Burcu Tezcan: Visualization, investigation. Bilgehan Güzel: Supervision. Yetkin Gök: Supervision, writing-reviewing and editing. Tugba Taskin Tok: Software, validation. Aydın Aktaş and Yeliz Demir: Writing-reviewing and editing.

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Correspondence to Yetkin Gök.

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Demirci, Ö., Tezcan, B., Demir, Y. et al. Acetylphenyl-substituted imidazolium salts: synthesis, characterization, in silico studies and inhibitory properties against some metabolic enzymes. Mol Divers 27, 2767–2787 (2023). https://doi.org/10.1007/s11030-022-10578-3

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