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Development of indanones and isatins as non-cytotoxic inhibitors of cholinesterases

Josephine M. Gießel, Anne Loesche, Sophie Hoenke, Immo Serbian, Ahmed Al-Harrasi, Rene Csuk

Abstract


A small library of indanone-amides and substituted isatin derivatives has been prepared; these compounds have been investigated for their ability to act as inhibitors for the enzymes acetyl- and butyrylcholinesterase (AChE, BChE). Several of them were moderate inhibitors for AChE and not cytotoxic for a variety of human tumor cell lines as well as for non-malignant mouse fibroblasts. In this library consisting of 49 derivatives, 5,7-dibromo-4-iodoisatin was shown to be a good mixed-type inhibitor for AChE (K­i = 2.52 ± 0.61 µM and K = 11.74 ± 1.31 µM) but this compound also acted as a dual inhibitor for BChE (Ki = 4.49 ± 0.32 µM and K = 6.56 ± 0.57 µM). Interestingly, N-hexyl-1-oxo-2,3-dihydro-1H-indene-2-carboxamide was cytotoxic especially for MCF-7 breast adenocarcinoma cells (EC50 = 4.28 ± 0.5 µM).


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References


- I. Łozińska, A. Świerczyńska, Z. Molęda, A. M. Hartman, A. K. H. Hirsch, Z. Czarnocki, Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments, Arch. Pharm., 2018, 1800194.

- P. Costanzo, L. Cariati, D. Desiderio, R. Sgammato,

A. Lamberti, R. Arcone, R. Salerno, M. Nardi, M. Masullo, M. Oliverio, Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors, ACS Med. Chem. Lett., 2016, 7, 470-475.

- K. O. Yerdelen, M. Koca, B. Anil, H. Sevindik, Z. Kasap, Z. Halici, K. Turkaydin, G. Gunesacar, Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer’s disease, Bioorg. Med. Chem. Lett., 2015, 25, 5576-5582.

- M. Koca, K. O. Yerdelen, B. Anil, Z. Kasap, H. Sevindik, I. Ozyurek, G. Gunesacar, K. Turkaydin, Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents, J. Enzyme Inhib. Med. Chem., 2016, 31, 13-23.

- M. S. Altowyan, M. Ali, S. M. Soliman, A. M. Al-Majid, M. S. Islam, S, Yousuf, M. I. Choudhary, H. A. Ghabbour, A. Barakat, Synthesis, computational studies and biological activity of oxamohydrazide derivatives bearing isatin and ferrocene scaffolds, J. Mol. Struct., 2020, 1202, 127372.

- A. V. Bogdanov, I. F. Zaripova, A. D. Voloshina, A. S. Sapunova, N. V. Kulik, I. V. Tsivunina, A. B. Dorbrynin, V. F. Mironov, J. Fluorine Chem., 2019, 227, 109345.

- M. M. H. Arief, W. I. A. El-Dougdoug, M. A. Sayed, Synthesis of some new isatin derivatives of expected biological activities, J. Basic Environm. Sci., 2019, 6, 149-155.

- T. Sandmeyer, Über Isonitrosoacetanilide und deren Kondensation zu Isatinen, Helv. Chim. Acta, 1919, 2, 234-242.

- Y. S. Tingare, M. T. Shen, C. Su, S. Y. Ho, S. H. Tsai, B. -R. Chen, W. R. Li, Novel Oxindole Based Sensitizers: Synthesis and Application in Dye-Sensitized Solar Cells, Org. Lett., 2013, 15, 4292-4295.

- J. B. Campbell, E. J. Warawa, Preparation and formulation of heterocyclic fused tricyclic compounds as anxiolytics, EP245053A119871111.

- L. -S. Feng, M. -L. Liu, S. Zhang, Y. Chai, B. Wang, Y.-B. Zhang, K. Lv, Y. Guan, H. -Y. Guo, C. -L. Xiao, Synthesis and in vitro antimycobacterial activity of 8-OCH3 ciprofloxacin methylene and ethylene isatin derivatives, Eur. J. Med. Chem., 2011, 46, 341-348.

- Z. Wang, C. Wang, Y. Sun, N. Zhang, Z. Liu, J. Liu, A novel strategy to the synthesis of 4-anilinoquinazoline derivatives, Tetrahedron, 2014, 70, 906-913.

- P. Polychronopoulos, P. Magiatis, A. L. Skaltsounis, V. Myrianthopoulos, E. Mikros, A. Tarricone, A. Musacchio, S.M. Roe, L. Pearl, M. Leost, P. Greengard, L. Meijer, Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases, J. Med. Chem., 2004, 47, 935-946.

- G. L. Ellman, K. D. Courtney, V. J. Andres, R. M. Featherstone, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol., 1961, 7, 88-95.

- A. Loesche, A. Kowitsch, R. Csuk, S. D. Lucas, Z. Al-Halabi, W. Sippl, A. Al-Harrasi, Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential, Bioorg. Chem., 2018, 85, 23-32.

- S. Liu, W. Wei, Y. Li, X. Liu, X. Cao, K. Lei, M. Zhou, Design, synthesis, biological evaluation and molecular docking studies of phenylpropanoid derivatives as potent anti-hepatitis B virus agents, Eur. J. Med. Chem., 2015, 95, 473-482.

- Suresh, D. Kumar, J. S. Sandhu, Bismuth(III) Chloride–Mediated, Efficient, Solvent-Free, MWI-Enhanced Doebner Condensation for the Synthesis of (E)-Cinnamic Acids, Synth. Commun., 2010, 40, 1915-1919.

- T. Takahashi, M. Miyazawa, Tyrosinase inhibitory activities of cinnamic acid analogues, Pharmazie, 2010, 65, 913-918.

- K. Kindler, K. Lührs, Studien über den Mechanismus chemischer Reaktionen, XXII. (Über Hydrierungen und über spezifische Hydrierungen mittels gebundenen Wasserstoffs, VI). Hydrierungen mittels Terpenen, Ann. Chem., 1965, 685, 36-48.

- J. Koo, The Synthesis of 4,5,6-Trimethoxyindene- and 4,5,6-Trimethoxyindanecarboxylic Acids and Esters, J. Am. Chem. Soc., 1953, 75, 1889-1891.

- C. Pan, X. Zeng, Y. Guan, X. Jiang, L. Li, H. Zhang, Design and Synthesis of Brazilin-Like Compounds, Synlett, 2011, 425-429.

- T. M. Harris, C. R. Hauser, Benzylation at the Terminal Methyl Group of Certain Unsymmetrical β-Diketones Through One of Two Possible Intermediate Dicarbanions, J. Am. Chem. Soc., 1959, 81, 1160-1164.

- T. Dohi, N. Takenaga, A. Goto, H. Fujioka, Y. Kita, Clean and Efficient Benzylic C−H Oxidation in Water Using a Hypervalent Iodine Reagent: Activation of Polymeric Iodosobenzene with KBr in the Presence of Montmorillonite-K10, J. Org. Chem., 2008, 73, 7365-7368.

- A. Romeo, H. Corrodi, E. Hardegger, Umsetzungen des

o-Nitrophenylessigesters und des 2-Chlor-6-nitro-phenyl-brenztraubensäureesters, Helv. Chim. Acta, 1955, 38, 463-467.

- S. B. Kadin, Preparation and formulation of analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds, US4690943A19870901.

- M. E. Matheus, F. D. A. Violante, S. J. Garden, A. C. Pinto, P. D. Fernandes, Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line, Eur. J. Pharmacol., 2007, 556, 200-206.

- K. C. Joshi, V. N. Pathak, S. K. Jain, Studies of potential organo-fluorine antibacterial agents. Part 5: Synthesis and antibacterial activity of some new fluorine-containing indole-2,3-dione derivatives, Pharmazie, 1980, 35, 677-679.

- B. R. Baker, R. E. Schaub, J. P. Joseph, F. J. McEvoy, J. H. Williams, An antimalarial alkaloid from hydrangea. XV. Synthesis of 5-, 6-, 7-, and

-derivatives with two identical substituents, J. Org. Chem., 1952, 17, 149-156.

- L. Ettinger, P. Friedländer, Über 6.6′-Dibrom-indirubin, Ber. Dt. Chem. Ges., 1912, 45, 2081-2083.

- S. Inagaki, Diphenylisatin and its derivatives. IV. Monobromo derivatives of dianisoleisatin and its oxidation product, Yakugaku Zasshi, 1938, 58,

-975.

- A. Beauchard, H. Laborie, H. Rouillard, O. Lozach, Y. Ferandin, R. L. Guével, C. Guguen-Guillouzo, L. Meijer, T. Besson, V. Thiéry, Synthesis and kinase inhibitory activity of novel substituted indigoids, Bioorg. Med. Chem., 2009, 17, 6257-6263.

- F. Ziegler, T. Kappe, R. Salvador, Synthesen von Heterocyclen, 44. Mitt.: Eine Synthese des Isatins, Monatsh. Chem., 1963, 94, 453-459.

- C. A. Fetscher, M. T. Bogert, Researches on quinaolines. XLIV. The synthesis of some new quinazoline derivatives of veratrole akin to alkaloids, J. Org. Chem., 1939, 4, 71-87.

- J. Gray, D. R. Waring, 3-Amino-2,1-benzoisothiazole. Synthesis of some chloro and trifluoromethyl derivatives, J. Heterocycl. Chem., 1980, 17, 65-67.

- D. H. Klaubert, J. H. Sellstedt, C. J. Guinosso, R. J. Capetola, S. C. Bell, N-(Aminophenyl)oxamic acids and esters as potent, orally active antiallergy agents, J. Med. Chem., 1981, 24, 742-748.

- G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, A. J. Olson, AutoDock and AutoDockTools: Automated docking with selective receptor flexibility, J. Comput. Chem., 2009, 30, 2785-2791




DOI: http://dx.doi.org/10.13171/mjc10202002161233rc

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