SOME NOVEL SCHIFF BASE DERIVATIVES AS PROMISING CHOLINESTERASE INHIBITORS WITH ANTIOXIDANT ACTIVITY AGAINST ALZHEIMER’S DISEASE: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION

Year 2022, Volume: 8 Issue: 2, 138 - 146, 31.12.2022

Ercan Çınar Mehmet Boğa Giray Topal Reşit Çakmak

https://doi.org/10.51477/mejs.1204413

Cited By: 1

Abstract

In this manuscript, five novel Schiff base derivatives containing a pyrazolone ring and a sulfonate moiety (6-10) except for 9 were designed, obtained for the first time and characterized by three spectroscopic techniques. The inhibition performances of these moleucles synthesized in two steps against cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated. By DPPH and ABTS assays, antioxidant activities of these molecules were also examined. In AChE assay, compound 6 (95.87±1.59 % inhibition) inhibited this enzyme better than galanthamine (76.98±0.42 % inhibition). In BChE assay, compound 10 with 87.92±1.08% inhibition value in the series indicated the highest activity compared to galanthamine (76.30±0.28 % inhibition). In ABTS radical scavenging assay, compounds 7, 8 and 9 except for 6 and 10 indicated higher antioxidant activities compared to butylated hydroxytoluene (BHT). It is believed that these results may contribute to the design and synthesis of novel antioxidant agents, AChE and BChE inhibitors.

Keywords

Schiff base, Enzyme inhibitor, Antioxidant agent, Alzheimer’s disease.

References

• Jarosova, R., Niyangoda, S.S., Hettiarachchi, P., Johnson, M.A., “Impaired dopamine release and latent learning in Alzheimer’s disease model zebrafish”, ACS Chemical Neuroscience, 13, 2924-2931, 2022. doi.org/10.1021/acschemneuro.2c00484.
• Veluppal, A., “Differentiation of Alzheimer conditions in brain MR images using bidimensional multiscale entropy-based texture analysis of lateral ventricles”, Biomedical Signal Processing and Control, 78, 103974, 2022. doi.org/10.1016/j.bspc.2022.103974.
• Skovronsky, D.M., Lee, V.M.Y., Trojanowski, J. Q., “Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications”, Annual Review of Pathology: Mechanisms of Disease, 1, 151-170, 2006. doi.org/10.1146/annurev.pathol.1.110304.100113.
• Pievani, M., de Haan, W., Wu, T., Seeley, W.W., Frisoni, G.B., “Functional network disruption in the degenerative dementias”, The Lancet Neurology, 10, 829-843, 2011. doi.org/10.1016/S1474-4422(11)70158-2.
• Li, R., Zhang, C., Rao, Y., Yuan, T.F., “Deep brain stimulation of fornix for memory ımprovement in alzheimer’s disease: a critical review”, Ageing Research Reviews, 79, 101668, 2022. doi.org/10.1016/j.arr.2022.101668.
• Osmaniye, D., Ahmad, I., Sağlık, B.N., Levent, S., Patel, H.M., Ozkay, Y., Kaplancıklı, Z.A., “Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects”, Journal of Biomolecular Structure and Dynamics, 1-17, 2022. doi.org/10.1080/07391102.2022.2139762.
• Jindal, H., Bhatt, B., Sk, S., Singh Malik, J., “Alzheimer disease immunotherapeutics: then and now”, Human vaccines & immunotherapeutics”, 10, 2741-2743, 2014. doi.org/10.4161/21645515.2014.970959.
• Hardy, J., Bogdanovic, N., Winblad, B., Portelius, E., Andreasen, N., Cedazo- Minguez, A., Zetterberg, H., “Pathways to Alzheimer's disease”, Journal of Internal Medicine, 275, 296-303, 2014. doi.org/10.1111/joim.12192.
• Parihar, M.S., Hemnani, T., “Alzheimer’s disease pathogenesis and therapeutic interventions”, Journal of Clinical Neuroscience, 11, 456-467, 2004. doi.org/10.1016/j.jocn.2003.12.007.
• Parnetti, L., Mignini, F., Tomassoni, D., Traini, E., Amenta, F., “Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?”, Journal of the Neurological Sciences, 257, 264-269, 2007. doi.org/10.1016/j.jns.2007.01.043.
• [Başaran, E., Çakmak, R., Şentürk, M., Taskin‐Tok, T., “Biological activity and molecular docking studies of some N‐phenylsulfonamides against cholinesterases and carbonic anhydrase isoenzymes”, Journal of Molecular Recognition, 35, e2982, 2022.
• Craig, L.A., Hong, N.S., McDonald, R.J., “Revisiting the cholinergic hypothesis in the development of Alzheimer's disease”, Neuroscience & Biobehavioral Reviews, 35, 1397-1409, 2011. doi.org/10.1016/j.neubiorev.2011.03.001.
• [Cummings, J. L., Back, C., “The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease”, The American Journal of Geriatric Psychiatry, 6, S64-S78, 1998. doi.org/10.1097/00019442-199821001-00009.
• Rusanen, M., Kivipelto, M., Quesenberry Jr, C.P., Zhou, J., Whitmer, R.A., “Heavy smoking in midlife and long-term risk of Alzheimer disease and vascular dementia”, Archives of Internal Medicine, 171, 333-339, 2011. doi:10.1001/archinternmed.2010.393.
• Van Marum, R.J., “Current and future therapy in Alzheimer’s disease”, Fundamental & Clinical Pharmacology, 22(3), 265-274, 2008. doi.org/10.1111/j.1472-8206.2008.00578.x.
• Wilkinson, D.G., Francis, P.T., Schwam, E., Payne-Parrish, J., “Cholinesterase inhibitors used in the treatment of Alzheimer’s disease”, Drugs & Aging, 21, 453-478, 2004. doi.org/10.2165/00002512-200421070-00004.
• Dawson, G.R., Iversen, S.D., “The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory”, Behavioural Brain Research, 57, 143-153, 1993. doi.org/10.1016/0166-4328(93)90130-I.
• Grutzendler, J., Morris, J.C., “Cholinesterase inhibitors for Alzheimer’s disease”, Drugs, 61, 41-52, 2001. doi.org/10.2165/00003495-200161010-00005.
• Teixeira, J.P., de Castro, A.A., Soares, F.V., da Cunha, E.F., Ramalho, T.C., “Future therapeutic perspectives into the Alzheimer’s disease targeting the oxidative stress hypothesis”, Molecules, 24, 4410, 2019. doi.org/10.3390/molecules24234410.
• Markesbery, W.R., “Oxidative stress hypothesis in Alzheimer's disease”, Free Radical Biology and Medicine, 23, 134-147, 1997. doi.org/10.1016/S0891-5849(96)00629-6.
• Leeuwenburgh, C., Heinecke, J.W., “Oxidative stress and antioxidants in exercise”, Current Medicinal Chemistry, 8, 829-838, 2001. doi.org/10.2174/0929867013372896.
• Rao, A.V., Balachandran, B., “Role of oxidative stress and antioxidants in neurodegenerative diseases”, Nutritional Neuroscience, 5, 291-309, 2002. doi.org/10.1080/1028415021000033767.
• Kerru, N., Gummidi, L., Maddila, S., Gangu, K.K., Jonnalagadda, S.B., “A review on recent advances in nitrogen-containing molecules and their biological applications”, Molecules, 25, 1909, 2020. doi.org/10.3390/molecules25081909.
• Raman, N., Johnson Raja, S., Sakthivel, A., “Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review”, Journal of Coordination Chemistry, 62, 691-709, 2009. doi.org/10.1080/00958970802326179.
• Başaran, E., Çakmak, R., Akkoç, S., Kaya, S., “Combined experimental and theoretical analyses on design, synthesis, characterization, and in vitro cytotoxic activity evaluation of some novel imino derivatives containing pyrazolone ring”, Journal of Molecular Structure, 1265, 133427, 2022. doi.org/10.1016/j.molstruc.2022.133427.
• Çakmak, R., Başaran, E., Şentürk, M., “Synthesis, characterization, and biological evaluation of some novel Schiff bases as potential metabolic enzyme inhibitors”, Archiv der Pharmazie, 355, 2100430, 2022. doi.org/10.1002/ardp.202100430.
• Çakmak, R., Başaran, E., Boğa, M., Erdoğan, Ö., Çınar, E., Çevik, Ö., “Schiff base derivatives of 4-aminoantipyrine as promising molecules: synthesis, structural characterization, and biological activities”, Russian Journal of Bioorganic Chemistry, 48, 334-344, 2022. doi.org/10.1134/S1068162022020182.
• Başaran, E., “Some aryl sulfonyl ester-based heterocyclic schiff bases: synthesis, structure elucidation and antioxidant activity”, Journal of the Institute of Science and Technology, 11, 2967-2978, 2021. doi.org/10.21597/jist.963129.
• Çınar, E., Başaran, E., Erdoğan, Ö., Çakmak, R., Boğa, M., Çevik, Ö., “Heterocyclic Schiff base derivatives containing pyrazolone moiety: Synthesis, characterization, and in vitro biological studies”, Journal of the Chinese Chemical Society, 68, 2355-2367, 2021. doi.org/10.1002/jccs.202100357.
• Alam, M.S., Lee, D.U., Bari, M., “Antibacterial and cytotoxic activities of Schiff base analogues of 4-aminoantipyrine”, Journal of the Korean Society for Applied Biological Chemistry, 57, 613-619, 2014. doi.org/10.1007/s13765-014-4201-2.
• Esmer, Y.İ., Çınar, E., Başaran, E., “Design, docking, synthesis and biological evaluation of novel nicotinohydrazone derivatives as potential butyrylcholinesterase enzyme inhibitör”, ChemistrySelect, 7, e202202771, 2022. doi.org/10.1002/slct.202202771.
• Ellman, G.L., Courtney, K.D., Andres Jr, V., Featherstone, R.M., “A new and rapid colorimetric determination of acetylcholinesterase activity”, Biochemical Pharmacology, 7, 88-90, 1961. doi.org/10.1016/0006-2952(61)90145-9.
• Çakmak, R., Çınar, E., Başaran, E., Boğa, M., “Synthesis, characterization and biological evaluation of ester derivatives of 4-(diethylamino) salicylaldehyde as cholinesterase, and tyrosinase inhibitors”, Middle East Journal of Science, 7, 137-144, 2021. doi.org/10.51477/mejs.947973.
• Blois, M.S., "Antioxidant determinations by the use of a stable free radical”, Nature, 181, 1199-1200, 1958. doi.org/10.1038/1811199a0.
• Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., Rice-Evans, C., “Antioxidant activity applying an improved ABTS radical cation decolorization assay”, Free Radical Biology and Medicine, 26, 1231–1237, 1999. doi.org/10.1016/S0891-5849(98)00315-3.