Synthesis of novel Schiff base derivatives of tacrine and investigation of their acetylcholinesterase inhibition potency
DOI:
https://doi.org/10.20450/mjcce.2019.1561Keywords:
Inhibition, acetylcholinesterase, tacrine, Schiff base, inhibition typeAbstract
Investigation of acetylcholinesterase (AChE) inhibition potency of some new Schiff base derivatives of tacrine (9-amino-1,2,3,4-tetrahydroacridine) was reported in this paper. Novel Schiff base derivatives of tacrine (3a–g) have been synthesized, and they have been characterized by several methods (FT-IR, 1H-NMR, 13C-NMR, etc.). Then, inhibition effects on AChE by the synthesized compounds have been investigated by the spectrophotometric Ellman method. IC50, Ki, KM and Vmax values and inhibition types have been determined. It was seen that all compounds had the property of a water-soluble reversible AChE inhibitor. Structure 3a was found to be the most potent inhibitor, with the IC50 value of 22.1 ± 1.11 nM (tacrine's IC50 value was calculated as 34.1 nM).
References
H. Gocer, F. Topal, M. Topal, M. Küçük, D. Teke, İ. Gülçin, S. H. Alwasel, C. T. Supuran, Acetyl-cholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin, J. Enzyme Inhib. Med. Chem., 31 (3), 441–447 (2016).
DOI: https://doi.org/10.3109/14756366.2015.1036051
S. Akhondzadeh, M. Noroozian, M. Mohammadi, S. Ohadinia, A. H. Jamshidi, M. Khani, Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial, J. Clin. Pharm. Ther., 28 (1), 53–59 (2003).
DOI: https://doi.org/10.1046/j.1365-2710.2003.00463.x
A. Dişli, M. Gümüş, K. Ünal, N. Sarı, F. Arslan, New multifunctional agents and their inhibitory effects on the acetyl cholinesterase enzyme, Maced. J. Chem. Chem. Eng., 37 (1), 21–34 (2018).
DOI: http://dx.doi.org/10.20450/mjcce.2018.1334
A. Nordberg, A. L. Svensson, Cholinesterase inhibitors in the treatment of Alzheimer’s disease, Drug Safety, 19 (6), 465–480 (1998).
DOI: https://doi.org/10.2165/00002018-199819060-00004
S. Rizzo, C. Riviere, L. Piazzi, A. Bisi, S. Gobbi, M. Bartolini, V. Andrisano, F. Morroni, A. Tarozzi, J. P. Monti, A. Rampa, Benzofuran-based hybrid compounds for the inhibition of cholinesterase activity, β amyloid ag-gregation, and Aβ neurotoxicity, J. Med. Chem., 51 (10), 2883–2886 (2008). DOI: 10.1021/jm8002747
E. Aynacı, A. Yaşar, F. Arslan, An amperometric biosensor for acetylcholine determination prepared from acetylcholinesterase-choline oxidase immobilized in polypyrrole-polyvinylsulpfonate film, Sens Actuators B: Chem. 202, 1028–1036 (2014).
DOI: https://doi.org/10.1016/j.snb.2014.06.049
A. T. Tunç, E. Aynacı Koyuncu, F. Arslan, Development of an acetylcholinesterase-choline oxidase based biosensor for acetylcholine determination, Artif. Cells, Nanomed. and Biotechnol., 44 (7), 1–6 (2015). DOI: https://doi.org/10.3109/21691401.2015.1080167
J. Baek, H. L. Lee, K. S. Kang, K. H. Kim, Chemical constituents from the fruit of Citrus unshiu and their inhibitory effects on аcetylcholinesterase, Maced. J. Chem. Chem. Eng., 36 (1), 15–2 (2017).
DOI: http://dx.doi.org/10.20450/mjcce.2017.1139
D. Cör1, T. Botić, Ž. Knez, A. Gregori, F. Pohleven, The effects of different solvents on bioactive metabolites and “in vitro” antioxidant and anti-acetylcholinesterase activity of Ganoderma lucidum fruiting body and primordia extracts, Maced. J. Chem. Chem. Eng., 36 (1), 129–141 (2017).
DOI: http://dx.doi.org/10.20450/mjcce.2017.1054
P. T. Francis, A. M. Palmer, M. Snape, G. K. Wilcock, The cholinergic hypothesis of Alzheimer’s disease: a review of progress, J. Neurol. Neurosur. Ps. 66 (2), 137–147 (1999).
B. Halfon, E. Çiftçi, G. Topçu. Flavonoid constituents of Sideritis caesarea, Turk. J. Chem. 37, 464–472 (2013). DOI: 10.3906/kim-1206-45
J. C. Jaén, V. E. Gregor, C. Lee, R. Davis, M. Emmerling, Acetylcholinesterase inhibition by fused dihydroquinazoline compounds, Bioorg. Med. Chem. Lett., 6 (6), 737–742 (1996).
DOI: https://doi.org/10.1016/0960-894X(96)00102-3
M. Pohanka, Cholinesterases, a target of pharmacology and toxicology, Biomedical papers., 155 (3), 219–223 (2011). DOI: 10.5507/bp.2011.036
I. Silman, J. L. Sussman, Acetylcholinesterase: how is structure related to function?, Chem Biol Interact. 175, 3–10 (2008).
DOI: https://doi.org/10.1016/j.cbi.2008.05.035
M. Pohanka, J. Zdarova Karasova, K. Kuca, J. Pikula, Multichannel spectrophotometry for analysis of organophosphate paraoxon in beverages, Turk. J. Chem. 34, 91–98 (2010). DOI: 10.3906/kim-0903-7
Z. Kovarik, Z. Radic, H. A. Berman, V. Simeon-Rudolf, E. Reiner, P. Taylor, Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates, Biochem. J. 373, 33–40 (2003). DOI: 10.1042/bj20021862
C. Bartolucci, L. A. Haller, U. Jardis, G. Fels, D. Lamba, Probing Torpedo Californica acetyl¬cholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives, J Med Chem. 53, 745–51(2010). DOI: 10.1021/jm901296p
H. J. Kreienkamp, C. Weise, R. Raba, A. Aaviksaar, F. Hucho, Anionic subsites of the catalytic center of acetylcholinesterase from Torpedo and from cobra venom, Proc. Natl. Acad. Sci. USA., 88, 6117–6121 (1991). DOI: https://doi.org/10.1073/pnas.88.14.6117
G. Orhan, İ. Orhan, N. Subutay-Öztekin, F. Ak, B. Şener, Contemporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer’s disease, Recent Patents on CNS Drug Discovery. 4, 43–51 (2009).
DOI: https://doi.org/10.2174/157488909787002582
H. Shaw, G. Bentley, Anticholinesterase properties of tetrahydroaminoacridine, Aust. J. Exp. Biol. 31, 573–578 (1953).
W. K. Summers, L. V. Majovski, G. M. Marsh, K. Tachiki, A. Kling, Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type, New Engl. J. Med., 315, 1241–1245 (1986).
DOI: 10.1056/NEJM198611133152001
M. Harel, I. Schalk, L. Ehret-Sabatier, F. Bouet, M. Goeldner, C. Hirth, P. H. Axelsen, I. Silman, J. L. Sussman, Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase, Proc. Natl. Acad. Sci., 90 (19), 9031–9035 (1993).
H. Khalid, A. U. Rehman, M. A. Abbasi, R. Hussain, K. M. Khan, M. Ashraf, S. A. Ejaz, M. Q. Fatmi, Synthesis, biological evaluation, and molecular docking of N'-(Aryl/alkylsulfonyl)-1-(phenylsulfonyl) piperidine-4-carbohydrazide derivatives, Turk. J. Chem, 38, 189–201 (2014). DOI: 10.3906/kim-1303-89
İ. Şakıyan, E. Aynacı Koyuncu, F. Arslan, H. Öğütçü, N. Sarı, Some novel antimicrobial therapeutic agents for acetylcholinesterase inhibitors; synthesis of hydroxy-quinoline ester involving amino acid, G. U. J. Sci. 28 (1), 11–19(2015).
D. Schuster, M. Spetea, M. Music, S. Rief, M. Fink, J. Kirchmair, J. Schütz, G. Wolber, T. Langer, H. Stuppner, et al., Morphinans and isoquinolines: acetyl¬cholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors, Bioorg. Med. Chem. 18, 5071–5080 (2010).
DOI: https://doi.org/10.1016/j.bmc.2010.05.071
S. Yılmaz, Y. Akbaba, B. Özgeriş, L. P. Köse, S. Göksu, İ. Gülçin, S. H. Alwasel, C. T. Supuran, Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase, J. Enzyme Inhib. Med. Chem., Early Online 1–8 (2016).
DOI: https://doi.org/10.3109/14756366.2016.1149477
B. Turan, K. Şendil, E. Şengül, M. S. Gültekin, P. Taslimi, İ. Gulçin, C. T. Supuran, The synthesis of some β-lactams and investigation of their metal-chelating activity, carbonic anhydrase and acetylcholinesterase inhibition profiles, J. Enzyme Inhib. Med. Chem. Early Online, 1–10 (2016).
DOI: https://doi.org/10.3109/14756366.2016.1170014
S. Singla, P. Piplani, Coumarin derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies, Bioorg. Med. Chem. 24, 4587–4599 (2016).
DOI: https://doi.org/10.1016/j.bmc.2016.07.061
M. I. Rodríguez-Franco, M. I. Fernández-Bachiller, C. Pérez, B. Hernández-Ledesma, B. Bartolomé, Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties, J. Med. Chem. 49, 459–462 (2006). DOI: 10.1021/jm050746d
M. I Fernández‐Bachiller, C. Pérez, N. E. Campillo, J. A. Páez, G. C. González‐Muñoz, P. Usan, E. García-Palomero, M. G. López, M. Villaroya, A. G. García, et al., Tacrine-melatonin hybrids as multifunctional agents for Alzheimer's disease, with cholinergic, antioxidant, and neuroprotective properties, Chem. Med. Chem., 4 (5), 828–841, (2009).
DOI: https://doi.org/10.1002/cmdc.200800414
L. Fang, B. Kraus, J. Lehmann, J. Heilmann, Y. Zhang, M. Decker, Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates, Bioorg. Med. Chem. Lett. 18, 2905–2909 (2008).
DOI: https://doi.org/10.1016/j.bmcl.2008.03.073
M. Benchekroun, M. Bartolini, J. Egea, A. Romero, E. Soriano, M. Pudlo, V. Luzet, V. Andrisano, M. N. Jimeno, M. G. Lopéz, et al., Novel tacrine‐grafted ugi adducts as multipotent anti‐Alzheimer drugs: A synthetic renewal in tacrine-ferulic acid hybrids, ChemMedChem., 10 (3), 523–539 (2015).
DOI: https://doi.org/10.1002/cmdc.201402409
M. Rosini, E. Simoni, M. Bartolini, A. Tarozzi, R. Matera, A. Milelli, Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer’s disease, Eur. J. Med. Chem. 46, 5435–5442 (2011).
DOI: https://doi.org/10.1016/j.ejmech.2011.09.001
Z. Liu, L. Fang, H. Zhang, S. Gou, L. Chen, Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property, Bioorg. Med. Chem. 25, 2387–2398 (2017). DOI: https://doi.org/10.1016/j.bmc.2017.02.049
G. L. Ellman, K. D. Courtney, V. Andres, R. M. Featherstone, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol. 7 (2), 88–95 (1961).
DOI: https://doi.org/10.1016/0006-2952(61)90145-9
W. Luo, Y. P. Li, Y. He, S. L. Huang, D. Li, L.Q. Gu, Z. S. Huang, Synthesis and evaluation of heterobivalent tacrine derivatives as potential multi-functional anti-Alzheimer agents, Eur. J. Med. Chem. 46 (6), 2609–2616 (2011).
DOI: https://doi.org/10.1016/j.ejmech.2011.03.058
Q. Xie, H. Wang, Z. Xia, M. Lu, W. Zhang, X. Wang, W. Zhou, Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-β aggregation, J. Med. Chem. 51 (7), 2027–2036 (2008). DOI: 10.1021/jm070154q
U. A. Mohsen, Studies on imidazopyridine derivatives as acetylcholinesterase inhibitors, Journal of Marmara University Institute of Health Sciences. 2 (3), 119–123 (2012).
E. Keha, İ. Küfrevioğlu, Biyokimya, 6th Edition, Aktif Yayınevi, İstanbul, 2009, pp. 93–95, 116–123.
L. Huang, Z. Luo, F. He, J. Lu, X. Li, Synthesis and biological evaluation of a new series of berberine deriva-tives as dual inhibitors of acetylcholinesterase and butyr-ylcholinesterase, Bioorgan. Med. Chem. 18 (12), 4475–4484 (2010).
DOI: https://doi.org/10.1016/j.bmc.2010.04.063
A. Rehman, A. Fatima, N. Abbas, M. A. Abbasi, K. M. Khan, M. Ashraf, I. Ahmad, S. A. Ejaz, Synthesis, characterization and biological screening of 5-substituted-1, 3, 4-oxadiazole-2yl-N-(2-methoxy-5-chlorophenyl)-2-sulfanyl acetamide, Pak. J. Pharm. Sci. 26(2) 345–352 (2013).
R. Raza, A. Saeed, M. Arif, S. Mahmood, M. Muddassar, A. Raza, J. Iqbal, Synthesis and biological evaluation of 3‐thiazolocoumarinyl schiff‐base derivatives as cholinesterase inhibitors, Chem. Biol. Drug. Des. 80 (4), 605–615 (2012).
DOI: https://doi.org/10.1111/j.1747-0285.2012.01435.x
N. S. Gwaram, H. M. Ali, M. A. Abdulla, M. J. Buckle, S. D. Sukumaran, L. Y. Chung, P. Hassandarvish, Syn-thesis, characterization, X-ray crystallography, acetyl cho-linesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide-derived Schiff bases, Molecules, 17 (3), 2408–2427 (2012).
