Login Register Cart 0
Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Green Synthesis and Acetylcholinesterase Inhibition of Coumarin-1,2,4-Triazole Hybrids

Author(s): Maja Karnaš, Vesna Rastija*, Domagoj Šubarić and Maja Molnar

Volume 27, Issue 10, 2023

Published on: 08 September, 2023

Page: [883 - 892] Pages: 10

DOI: 10.2174/1385272827666230817145725

Price: $65

Abstract

The pursuit of biologically active compounds has led many researchers to synthesize different heterocyclic hybrids with prominent activity. Both coumarin and 1,2,4-triazole are very potent scaffolds whose hybrids have improved biological activities.

This study synthesized twenty-one new coumarin-1,2,4-triazole hybrids in a one-step reaction using choline chloride : urea deep eutectic solvent. The green approach to this synthesis has led to shorter reaction times, higher yields, and purity of final compounds.

The title compounds were characterized and screened for drug-likeness parameters to evaluate their viability as potential drug candidates and for their in vitro acetylcholinesterase inhibitory activity. All tested compounds complied with the drug-likeness rules. However, they exhibited only weak to moderate inhibitory activity against acetylcholinesterase.

Molecular docking analysis revealed that title compounds mostly bind to the peripheral anionic region of the acetylcholinesterase active site, therefore hindering, but not completely obstructing, substrate from entering the enzyme catalytic site.

« Previous
Graphical Abstract

[1]
Sahu, J.K.; Ganguly, S.; Kaushik, A. Triazoles: A valuable insight into recent developments and biological activities. Chin. J. Nat. Med., 2013, 11(5), 456-465.
[http://dx.doi.org/10.1016/S1875-5364(13)60084-9] [PMID: 24359767]
[2]
Ünver, Y. Düğdü, E.; Sancak, K.; Er, M.; Karaoğlu, S.A. Synthesis and antimicrobial and antitumor activity of some new [1,2,4] triazole-5-one derivatives. Turk. J. Chem., 2009, 33, 135-147.
[http://dx.doi.org/10.3906/kim-0804-8]
[3]
Jacob, J.H.; Irshaid, F.I.; Al-Soud, Y.A. Antibacterial activity of some selected 1,2,4-triazole derivatives against standard, environmental, and medical bacterial strains. Adv. Stud. Biol., 2013, 5, 291-301.
[http://dx.doi.org/10.12988/asb.2013.3418]
[4]
Xu, J.; Cao, Y.; Zhang, J.; Yu, S.; Zou, Y.; Chai, X.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives. Eur. J. Med. Chem., 2011, 46(7), 3142-3148.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.042] [PMID: 21420761]
[5]
Kumudha, D.; Leonard, J.T.; Muthumani, M.; Chidhambaranathan, N.; Kalavathi, T. Synthesis and evaluation of some 1,2,4-triazole derivatives as anticonvulsant, anti-inflammatory and antimicrobial agents. Asian J. Pharm. Clin. Res., 2013, 6, 5-8.
[6]
Sztanke, K.; Tuzimski, T.; Rzymowska, J.; Pasternak, K. Kandefer-Szerszeń M. Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives. Eur. J. Med. Chem., 2008, 43(2), 404-419.
[http://dx.doi.org/10.1016/j.ejmech.2007.03.033] [PMID: 17531354]
[7]
Labanauskas, L.; Udrenaite, E.; Gaidelis, P.; Brukštus, A. Synthesis of 5-(2-,3- and 4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol derivatives exhibiting anti-inflammatory activity. Farmaco, 2004, 59(4), 255-259.
[http://dx.doi.org/10.1016/j.farmac.2003.11.002] [PMID: 15081342]
[8]
Küçükgüzel, Ş.G.; Çıkla-Süzgün, P. Recent advances bioactive 1,2,4- triazole-3-thiones. Eur. J. Med. Chem., 2015, 97, 830-870.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.033] [PMID: 25563511]
[9]
Arfan, M.; Siddiqui, S.Z.; Abbasi, M.A.; Rehman, A.; Shah, S.A.A.; Ashraf, M.; Rehman, J.; Saleem, R.S.Z.; Khalid, H.; Hussain, R.; Khan, U. Synthesis, in vitro and in silico studies of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols as cholinesterase inhibitors. Pak. J. Pharm. Sci., 2018, 31(6), 2697-2708.
[PMID: 30587482]
[10]
Mehr-un-Nisa Munawar, M.A.; Chattha, F.A.; Kousar, S.; Munir, J.; Ismail, T.; Ashraf, M.; Khan, M.A. Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors. Bioorg. Med. Chem., 2015, 23(17), 6014-6024.
[http://dx.doi.org/10.1016/j.bmc.2015.06.051] [PMID: 26189031]
[11]
Pereira, T.M.; Franco, D.P.; Vitorio, F.; Kummerle, A.E. Coumarin Compounds in medicinal chemistry: Some important examples from the last years. Curr. Top. Med. Chem., 2018, 18(2), 124-148.
[http://dx.doi.org/10.2174/1568026618666180329115523] [PMID: 29595110]
[12]
Zhang, L.; Xu, Z. Coumarin-containing hybrids and their anticancer activities. Eur. J. Med. Chem., 2019, 181, 111587.
[http://dx.doi.org/10.1016/j.ejmech.2019.111587] [PMID: 31404864]
[13]
Yusufzai, S.K.; Khan, M.S.; Sulaiman, O.; Osman, H.; Lamjin, D.N. Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease. Chem. Cent. J., 2018, 12(1), 128.
[http://dx.doi.org/10.1186/s13065-018-0497-z] [PMID: 30515636]
[14]
de Souza, L.G.; Rennó, M.N.; Figueroa-Villar, J.D. Coumarins as cholinesterase inhibitors: A review. Chem. Biol. Interact., 2016, 254, 11-23.
[http://dx.doi.org/10.1016/j.cbi.2016.05.001] [PMID: 27174134]
[15]
Reddy, K.R.; Mamatha, R.; Babu, M.S.S.; Shiva Kumar, K.; Jayaveera, K.N.; Narayanaswamy, G. Synthesis and antimicrobial activities of some triazole, thiadiazole, and oxadiazole substituted coumarins. J. Heterocycl. Chem., 2014, 51(1), 132-137.
[http://dx.doi.org/10.1002/jhet.1745]
[16]
Panda, S.S.; Malik, R.; Chand, M.; Jain, S.C. Synthesis and antimicrobial activity of some new 4-triazolylmethoxy-2H-chromen-2-one derivatives. Med. Chem. Res., 2012, 21(11), 3750-3756.
[http://dx.doi.org/10.1007/s00044-011-9881-0]
[17]
Shi, Y.; Zhou, C.H. Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents. Bioorg. Med. Chem. Lett., 2011, 21(3), 956-960.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.059] [PMID: 21215620]
[18]
Singh, A.; Sharma, S.; Arora, S.; Attri, S.; Kaur, P.; Kaur Gulati, H.; Bhagat, K.; Kumar, N.; Singh, H.; Vir Singh, J.; Mohinder Singh Bedi, P. New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation. Bioorg. Med. Chem. Lett., 2020, 30(20), 127477.
[http://dx.doi.org/10.1016/j.bmcl.2020.127477] [PMID: 32781220]
[19]
Chekir, S.; Debbabi, M.; Regazzetti, A.; Dargère, D.; Laprévote, O.; Ben Jannet, H.; Gharbi, R. Design, synthesis and biological evaluation of novel 1,2,3-triazole linked coumarinopyrazole conjugates as potent anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase and anti-cancer agents. Bioorg. Chem., 2018, 80, 189-194.
[http://dx.doi.org/10.1016/j.bioorg.2018.06.005] [PMID: 29940340]
[20]
Pourabdi, L. Küçükkılınç, T.T.; Khoshtale, F.; Ayazgök, B.; Nadri, H.; Farokhi Alashti, F.; Forootanfar, H.; Akbari, T.; Shafiei, M.; Foroumadi, A.; Sharifzadeh, M.; Shafiee Ardestani, M.; Abaee, M.S.; Firoozpour, L.; Khoobi, M.; Mojtahedi, M.M. Synthesis of new 3-arylcoumarins bearing n-benzyl triazole moiety: Dual lipoxygenase and butyrylcholinesterase inhibitors with anti-amyloid aggregation and neuroprotective properties against alzheimer’s disease. Front Chem., 2022, 9, 810233.
[http://dx.doi.org/10.3389/fchem.2021.810233] [PMID: 35127652]
[21]
Massoulié, J.; Pezzementi, L.; Bon, S.; Krejci, E.; Vallette, F.M. Molecular and cellular biology of cholinesterases. Prog. Neurobiol., 1993, 41(1), 31-91.
[http://dx.doi.org/10.1016/0301-0082(93)90040-Y] [PMID: 8321908]
[22]
McGleenon, B.M.; Dynan, K.B.; Passmore, A.P. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br. J. Clin. Pharmacol., 1999, 48(4), 471-480.
[http://dx.doi.org/10.1046/j.1365-2125.1999.00026.x] [PMID: 10583015]
[23]
Mladenović M.; Arsić B.; Stanković N.; Mihović N.; Ragno, R.; Regan, A.; Milićević J.; Trtić-Petrović T.; Micić R. The targeted pesticides as acetylcholinesterase inhibitors: Comprehensive cross-organism molecular modelling studies performed to anticipate the pharmacology of harmfulness to humans in vitro the targeted. Molecules, 2018, 23(9), 2192.
[http://dx.doi.org/10.3390/molecules23092192] [PMID: 30200244]
[24]
Abdelli, A.; Azzouni, S.; Plais, R.; Gaucher, A.; Efrit, M.L.; Prim, D. Recent advances in the chemistry of 1,2,4-triazoles: Synthesis, reactivity and biological activities. Tetrahedron Lett., 2021, 86, 153518.
[http://dx.doi.org/10.1016/j.tetlet.2021.153518]
[25]
Holm, S.C.; Straub, B.F. Synthesis of N -substituted 1,2,4-triazoles. A review. Org. Prep. Proced. Int., 2011, 43(4), 319-347.
[http://dx.doi.org/10.1080/00304948.2011.593999]
[26]
Paiva, A.; Craveiro, R.; Aroso, I.; Martins, M.; Reis, R.L.; Duarte, A.R.C. Natural deep eutectic solvents-solvents for the 21st century. ACS Sustain. Chem.& Eng., 2014, 2(5), 1063-1071.
[http://dx.doi.org/10.1021/sc500096j]
[27]
Molnar, M.; Periš, I.; Komar, M. Choline chloride based deep eutectic solvents as a tuneable medium for synthesis of coumarinyl 1,2,4-triazoles: Effect of solvent type and temperature. Eur. J. Org. Chem., 2019, 2019(15), 2688-2694.
[http://dx.doi.org/10.1002/ejoc.201900249]
[28]
Čačić, M.; Trkovnik, M.; Čačić, F. Has-Schon, E. Synthesis and antimicrobial activity of some derivatives of (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide. Molecules, 2006, 11(2), 134-147.
[http://dx.doi.org/10.3390/11010134] [PMID: 17962784]
[29]
Walters, W.P.; Murcko, M.A. Prediction of ‘drug-likeness’. Adv. Drug Deliv. Rev., 2002, 54(3), 255-271.
[http://dx.doi.org/10.1016/S0169-409X(02)00003-0] [PMID: 11922947]
[30]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[31]
Kerns, E.H.; Di, L. Lipophilicity.Drug-like Properties: Concepts, Structure Design, and Methods: From ADME to Toxicity Optimization; Academic Press: Amsterdam, 2016, pp. 43-47.
[32]
Padrón, J.A.; Carrasco, R.; Pellón, R.F. Molecular descriptor based on a molar refractivity partition using Randic-type graph-theoretical invariant. J. Pharm. Sci., 2002, 5(3), 258-266.
[33]
Ertl, P.; Rohde, B.; Selzer, P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J. Med. Chem., 2000, 43(20), 3714-3717.
[http://dx.doi.org/10.1021/jm000942e] [PMID: 11020286]
[34]
Prasanna, S.; Doerksen, R. Topological polar surface area: A useful descriptor in 2D-QSAR. Curr. Med. Chem., 2009, 16(1), 21-41.
[http://dx.doi.org/10.2174/092986709787002817] [PMID: 19149561]
[35]
Veber, D.F.; Johnson, S.R.; Cheng, H.Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem., 2002, 45(12), 2615-2623.
[http://dx.doi.org/10.1021/jm020017n] [PMID: 12036371]
[36]
Ali, J.; Camilleri, P.; Brown, M.B.; Hutt, A.J.; Kirton, S.B. In silico prediction of aqueous solubility using simple QSPR models: The importance of phenol and phenol-like moieties. J. Chem. Inf. Model., 2012, 52(11), 2950-2957.
[http://dx.doi.org/10.1021/ci300447c] [PMID: 23121381]
[37]
Bajda, M. Więckowska, A.; Hebda, M.; Guzior, N.; Sotriffer, C.; Malawska, B. Structure-based search for new inhibitors of cholinesterases. Int. J. Mol. Sci., 2013, 14(3), 5608-5632.
[http://dx.doi.org/10.3390/ijms14035608] [PMID: 23478436]
[38]
Hansen, R.A.; Gartlehner, G.; Webb, A.P.; Morgan, L.C.; Moore, C.G.; Jonas, D.E. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis. Clin. Interv. Aging, 2008, 3(2), 211-225.
[http://dx.doi.org/10.2147/cia.S12159936] [PMID: 18686744]
[39]
Kryger, G.; Silman, I.; Sussman, J.L. Structure of acetylcholinesterase complexed with E2020 (Aricept®): Implications for the design of new anti-Alzheimer drugs. Structure, 1999, 7(3), 297-307.
[http://dx.doi.org/10.1016/S0969-2126(99)80040-9] [PMID: 10368299]
[40]
Sokol, I.; Toma, M. Krnić M.; Macan, A.M.; Drenjančević D.; Liekens, S.; Raić-Malić S.; Gazivoda Kraljević T. Transition metal-catalyzed synthesis of new 3-substituted coumarin derivatives as antibacterial and cytostatic agents. Future Med. Chem., 2021, 13(21), 1865-1884.
[http://dx.doi.org/10.4155/fmc-2021-0161] [PMID: 34533068]
[41]
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(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[42]
Molinspiration Cheminformatics. . Available from: https://www. molinspiration.com (Accessed December 7, 2022).
[43]
Ellman, G.L.; Courtney, K.D.; Andres, V., Jr; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7(2), 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[44]
Rastija, V. Vrandečić K.; Ćosić J.; Šarić G.K.; Majić I.; Agić D.; Šubarić D.; Karnaš, M.; Bešlo, D.; Komar, M.; Molnar, M. Effects of coumarinyl schiff bases against phytopathogenic fungi, the soil-beneficial bacteria and entomopathogenic nematodes: Deeper insight into the mechanism of action. Molecules, 2022, 27(7), 2196.
[http://dx.doi.org/10.3390/molecules27072196] [PMID: 35408596]
[45]
Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4(1), 17.
[http://dx.doi.org/10.1186/1758-2946-4-17] [PMID: 22889332]
[46]
Yang, J.M. Development and evaluation of a generic evolutionary method for protein-ligand docking. J. Comput. Chem., 2004, 25(6), 843-857.
[http://dx.doi.org/10.1002/jcc.20013] [PMID: 15011256]
[47]
Dassault Systèmes, B.I. Discovery Studio Visualizer; Release 2019; Dassault Systèmes: San Diego, CA, USA, 2019.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy