New multifunctional agents and their inhibitory effects on the acetyl cholinesterase enzyme

Authors

  • Ali Dişli Department of Chemistry, Faculty of Science, Gazi University, 06500 Teknikokullar, Ankara
  • Murat Gümüş Department of Chemistry, Faculty of Science, Gazi University, 06500 Teknikokullar, Ankara
  • Kübra Önal Department of Chemistry, Faculty of Science, Gazi University, 06500 Teknikokullar, Ankara, TURKİYE
  • Nurşen Sarı Department of Chemistry, Faculty of Science, Gazi University, 06500 Teknikokullar, Ankara, TURKİYE
  • Fatma Arslan Department of Chemistry, Faculty of Science, Gazi University, 06500 Teknikokullar, Ankara, TURKİYE

DOI:

https://doi.org/10.20450/mjcce.2018.1334

Keywords:

Alzheimer's disease, tetrazole, inhibition

Abstract

A novel series of 2-((-1-substituted phenyl-1H-tetrazol-5-yl)thio)-2,3-dihydro-1H-inden-1-one compounds were designed, synthesized, and evaluated as multi-potent anti-Alzheimer drug candidates. First, treatment of various organic isothiocyanates with sodium azide in the presence of pyridine gave corresponding 1-substituted phenyl-1H-tetrazol-5-thiol compounds. Then, novel 2-((-1-substituted phenyl-1H-tetrazol-5-yl)thio)-2,3-dihydro-1H-inden-1-one compounds were synthesized by treatment of 2,3-dihydro-1H-inden-1-one with the 1-substituted phenyl-1H-tetrazol-5-thiol in the presence of I2. The synthesized compounds were characterized by spectroscopic methods. The inhibitory effects of the synthesized compounds on the acetyl cholinesterase enzyme (AChE) were then tested. An o-iodo substituent displayed higher activity compared to the other analogs. The o-iodo substituent showed a mixed-type of the AChE with an IC50 value of 1.75 μM. For the studied compunds all IC50 values for AChE were in the  micromolar range.

References

REFERENCES

P. Kasa, H. Papp, P.J.R. Kasa, I. Torok, Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain, Neuroscience, 101, 89-100 (2000).

R.T. Bartus, R.L. Dean III, B. Beer, A.S. Lippa, The cholinergic hypothesis of geriatric memory dysfunctions. Science, 217, 408-417 (1982).

A. Singh, Alzheimer's disease Inhibitors: Current status and future prospects. Int. J. Pharmaceutical Life Sci., 5, 3734-3740 (2014).

A. Badia, J.E. Banos, P. Camps, Synthesis and evaluation of tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer’s disease. Bioorg. and Med. Chem., 6, 427–440 (1998).

S. Roman, A. Badia, P. Camps, M.V. Clos, Potentiation effects of (+/-)huprine X, a new acetylcholinesterase inhibitor, on nicotinic receptors in rat cortical synaptosomes. Neuropharmacology, 46, 95–102 (2004).

A. Castro, A. Martinez, Peripheral and dual binding site acetylcholinesterase inhibitors: implications in treatment of Alzheimer's disease. Mini Rev. Med.Chem. 1 267-272 (2001).

H. Sugimoto, H. Ogura, Y. Arai, Y. Iimura, Y. Yamanishi, Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor, Jap. J. Pharmacol., 89, 7-20 (2002).

R.N. Butler, Recent advances in tetrazole chemistry, Adv. Heterocycl. Chem., 21, 323-435 (1977).

J. Roh, K. Vávrová, A. Hrabálek. Synthesis and Functionalization of 5-Substituted Tetrazoles, Eur. J. Organic Chem., 6101-6118 (2012).

A. Dişli, G.D Celik, Y. Oner, L. Açık, Synthesis of some novel amino and thiotetrazole purine derivatives and investigation of their antimicrobial activity and DNA interactions, Med. Chem. Res., 22, 1470-1479 (2013).

R.C. Elderfield, Tetrazoles, Tetrazines and Purines and Related Ring Systems. New York: John Wiley & Sons Inc. 2-105 (1981).

T.L. Gilchrist, Pyrazoles, Triazoles, and Tetrazoles Heterocyclic Chemistry. Cambridge: Cambridge University Press, 195-204 (1976).

P.L. Ornstein, M.B. Arnold, N.K. Allen, T. Bleisch, P.S. Borromeo, C.W. Lugar, J.D. Leander, D. Lodge, D.D. Schoepp, Structure-Activity Studies of 6-(Tetrazolylalkyl)-Substituted Decahydroisoquinoline-3-carboxylic Acid AMPA Receptor Antagonists. 1. Effects of Stereochemistry, Chain Length, and Chain Substitution, J. Med. Chem., 39, 2219-2231 (1996).

R.J. Herr, 5-Substituted-1H-tetrazoles as Carboxylic Acid Isosteres: Medicinal Chemistry and Synthetic Methods, Bioorg. Med. Chem., 10, 3379-3393 (2002).

S. Saglam, A. Disli, Y. Erdogdu, M. K. Marchewka, N. Kanagathara, B. Bay, M.T. Gulluoglu, , Synthesis, characterization and theoretical studies of 5-(benzylthio)-1-cylopentyl-1H-tetrazole, Spectrochim. Acta A. Mol. Biomol. Spectrosc., 135, 1011-1018 (2015).

M. Prokopowicz, P. Młynarz, P. Kafarski. Synthesis of phosphonate derivatives of 2,3-dihydroindene, Tetrahedron Lett., 50, 7314-7317 (2009).

L.-M. Yang, L. Shwu-Jiuan, Y. Tsang-Hsiung, L. Kuo-Hsiung, Synthesis of indan derivatives as mechanism-based inhibitors of dopamine β-hydroxylase, Bioorg. and Med. Chem., 941-944 (1995).

T. Neubert, A. S. Kawatkar, E. Martinborough, A. Termin U.S. Patent No. 605,174. Washington, D. C: U.S. Patent and Trademark Office, (2009).

S. Y. Han, J. W. Lee, H. J. Kim, Y. J. Kim, S. W. Lee, Y. S. Gyoung, A Facile One-Pot Synthesis of 1-Substituted Tetrazole-5-thiones, Bull. Korean Chem. Soc., 55-59 (2012).

H.W. Altland Smiles Rearrangement of 2-Tetrazolylthio-3-aminopyridines, J. Org. Chem., 3395-3399 (1976).

E. C. Lieber, N. Pillai, R. D. Hites, The Reaction of Nitrous Acid with 4-Substituted-Thiosemicarbazides, Can. J. Chem., 832-842 (1957).

E.C. Lieber, J. Ramachandran, Isomeric 5-(Substituted)aminothiatriazole and 1-Substituted-Tetrazolinethiones, Can. J. Chem., 101-109 (1959).

G.L. Ellmaan, K.D. Courtney, V.J. Andres, R.M. Featherstone, A new and rapid colorimetric determination of acetyl cholinesterase activity, Biochem. Pharmacol., 88-95, (1961).

A. Scozzafava, P. Kalın, C. T. Supuran, I. Gulcin, S.H. Alwase, The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII), J Enzyme Inhib Med Chem., 941-947 (2015).

H. Dvir, I. Silman, M. Harel, T. L. Rosenberry, J. L. Sussman, Acetylcholinesterase: From 3D Structure to Function, Chem Biol Interact. 187, 10–22 (2010).

V. Tello-Franco, M.C. Lozada-García, M. Soriano-García, Experimental and computational studies on the inhibition of acetylcholinesterase by curcumin and some of its derivatives, Curr. Comput. Aided Drug Des., 9, 289-298 (2013).

S. Liu, R. Shang, L. Shi, R. Zhou, J. He, D.C Wan, Design, synthesis, and evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors. Chem. Biol. Drug Des., 84, 169-174 (2014).

E. Aynacı, Ph.D, Gazi University Graduate School of Natural and Applıed Sciences, TR 2015.

H.-R. Liu, X.-Q. Huang, D.-H. Lou, X.-J. Liu, W.-K. Liu, Q.-A. Wang, Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B, Bioorg Med Chem. Lett., 22, 6124-6131 (2014).

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Published

2018-06-01

How to Cite

Dişli, A., Gümüş, M., Önal, K., Sarı, N., & Arslan, F. (2018). New multifunctional agents and their inhibitory effects on the acetyl cholinesterase enzyme. Macedonian Journal of Chemistry and Chemical Engineering, 37(1), 21–34. https://doi.org/10.20450/mjcce.2018.1334

Issue

Section

Organic Chemistry