SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF ESTER DERIVATIVES OF 4-(DIETHYLAMINO)SALICYLALDEHYDE AS CHOLINESTERASE, AND TYROSINASE INHIBITORS

Year 2021, Volume: 7 Issue: 2, 137 - 144, 30.12.2021

Reşit Çakmak , Ercan Çınar , Eyüp Başaran , Mehmet Boğa

https://doi.org/10.51477/mejs.947973

Cited By: 10

Abstract

Alzheimer's Disease (AD), one of the diseases that still has no a specific therapy, has become a major public health issue owing to the increasing population of the elderly, particularly in rich countries. Inhibitory of cholinesterase enzymes (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which hydrolyze acetylcholine (ACh) and butyrylcholine (BCh) neurotransmitters, have recently become a choice for therapy of this disease. Therefore, there is currently a great demand for novel enzyme inhibitors with desirable properties for applying in the treatment of AD. A series of ester derivatives of 4-(diethylamino)salicylaldehyde 1-5 were successfully prepared in present work, and structurally illuminated with FT-IR, 1H and 13C NMR spectroscopy. The inhibition properties of the title molecules on AChE, BChE, and tyrosinase enzymes were extensively investigated, respectively. Compound 1 indicated potent inhibitory properties against BChE with 87.28±0.87% inhibition better than galantamine (73.83±0.25 %inhibition) employed as standard. Compound 3 showed potent inhibitory effect against tyrosinase with 87.73±0.22 % inhibition, which are better than kojic acid utilized as standard. The obtained results clearly revealed that some of these enzyme inhibitors have the potential to be utilized as potent enzyme inhibitors in the future.

Keywords

Esters, Acetylcholinesterase, Butyrylcholinesterase, Tyrosinase.

References

• [1] Yokeş, M. B., “Molecular genetics of Alzheimer's Disease”, Journal of Cellular and Molecular Medicine, 6, 73-97, 2007.
• [2] Mesulam, M. M., Principles of behavioral and cognitive neurology. Oxford University Press, Oxford 2000.
• [3] Lleo, A., Greenberg, S. M., Growdon, J. H., “Current pharmacotherapy for Alzheimer's disease”, Annual Review of Medicine, 57, 513-533, 2006.
• [4] Flynn, B. L., Ranno, A. E., “Pharmacologic management of Alzheimer disease part II: Antioxidants, antihypertensives, and ergoloid derivatives”, Annals of Pharmacotherapy, 33, 188-197, 1999.
• [5] Yaari, R., Corey-Bloom, J., “Alzheimer's disease”, Seminars in Neurology, 27, 32-41, 2007.
• [6] Hanağası, H. A., “Demans kavramı ve hastaya yaklaşım. Klinik Gelişim, 23, 44-47 2010.
• [7] Özkay, Ü. D., The effect of some benzothiazole derivatives on the learning and memory parametres of streptozotocin model of alzheimer's disease in rats, Ph. D. thesis, Anadolu University, Eskişehir, TR, Eskişehir, 2009.
• [8] Kazancioglu, E. A., Senturk, M., “Synthesis of N-phenylsulfonamide derivatives and investigation of some esterase enzymes inhibiting properties”, Bioorganic Chemistry, 104, 104279, 2020.
• [9] Arslan, T., Ceylan, M. B., Baş, H., Biyiklioglu, Z., Senturk, M., “Design, synthesis, characterization of peripherally tetra-pyridine-triazole-substituted phthalocyanines and their inhibitory effects on cholinesterases (AChE/BChE) and carbonic anhydrases (hCA I, II and IX)”, Dalton Transactions, 49, 203-209, 2020.
• [10] Telpoukhovskaia, M. A., Patrick, B. O., Rodríguez-Rodríguez, C., Orvig, C., “In silico to in vitro screening of hydroxypyridinones as acetylcholinesterase inhibitors”, Bioorganic and Medicinal Chemistry Letters, 26, 1624-1628, 2016.
• [11] Bajda, M., Więckowska, A., Hebda, M., Guzior, N., Sotriffer, C. A., Malawska, B., “Structure-based search for new inhibitors of cholinesterases”, International Journal of Molecular Sciences, 14, 5608-5632, 2013.
• [12] Özil, M., Balaydın, H. T., Şentürk, M., “Synthesis of 5-methyl-2, 4-dihydro-3H-1, 2, 4-triazole-3-one’s aryl Schiff base derivatives and investigation of carbonic anhydrase and cholinesterase (AChE, BuChE) inhibitory properties”, Bioorganic Chemistry, 86, 705-713, 2019.
• [13] Rescigno, A., Sollai, F., Pisu, B., Rinaldi, A., Sanjust, E., “Tyrosinase inhibition: general and applied aspects”, Journal of Enzyme Inhibition and Medicinal Chemistry, 17, 207-218. 2002.
• [14] Loizzo, M. R., Tundis, R., Menichini, F., “Natural and synthetic tyrosinase inhibitors as antibrowning agents: an update”, Comprehensive Reviews in Food Science and Food Safety, 11(4), 378-398, 2012.
• [15] Różanowska, M., Sarna, T., Land, E. J., Truscott, T. G., “Free radical scavenging properties of melanin: interaction of eu-and pheo-melanin models with reducing and oxidising radicals” Free Radical Biology and Medicine, 26, 518-525, 1999.
• [16] Zolghadri, S., Bahrami, A., Hassan Khan, M. T., Munoz-Munoz, J., Garcia-Molina, F., Garcia-Canovas, F., Saboury, A. A., “A comprehensive review on tyrosinase inhibitors”, Journal of Enzyme Inhibition and Medicinal Chemistry, 34, 279-309, 2019.
• [17] Gillbro, J. M., Olsson, M. J., “The melanogenesis and mechanisms of skin‐lightening agents–existing and new approaches” International Journal of Cosmetic Science, 33, 210-221, 2011.
• [18] Plensdorf, S., Livieratos, M., Dada, N., “Pigmentation disorders: diagnosis and management” American Family Physician, 96, 797-804, 2017.
• [19] Kim, H., Choi, H. R., Kim, D. S., Park, K. C., Topical hypopigmenting agents for pigmentary disorders and their mechanisms of action. Annals of Dermatology, 24, 1, 2012.
• [20] Nicolaidou, E., Katsambas, A. D., “Pigmentation disorders: hyperpigmentation and hypopigmentation”, Clinics in Dermatology, 32, 66-72, 2014.
• [21] Pillaiyar, T., Manickam, M., Jung, S. H., “Recent development of signaling pathways inhibitors of melanogenesis”, Cellular Signaling, 40, 99-115, 2017.
• [22] Pillaiyar, T., Manickam, M., Jung, S. H., “Downregulation of melanogenesis: drug discovery and therapeutic options”, Drug Discovery Today, 22, 282-298, 2017.
• [23] Pillaiyar, T., Namasivayam, V., Manickam, M., Jung, S. H., “Inhibitors of melanogenesis: an updated review”, Journal of Medicinal Chemistry, 61, 7395-7418, 2018.
• [24] Smit, N., Vicanova, J., Pavel, S., “The hunt for natural skin whitening agents”, International Journal of Molecular Sciences, 10, 5326-5349, 2009.
• [25] Kwak, S. Y., Choi, H. R., Park, K. C., Lee, Y. S., “Kojic acid–amino acid amide metal complexes and their melanogenesis inhibitory activities”, Journal of Peptide Science, 17, 791-797, 2011.
• [26] Topal, G., Tombak, A., Yigitalp, E., Batibay, D., Kilicoglu, T., Ocak, Y. S. (2017). Diester molecules for organic-based electrical and photoelectrical devices”, Journal of Electronic Materials, 46(7), 3958-3964.
• [27] Takahashi, T., Hijikuro, I., Sugimoto, H., Kihara, T., Shimmyo, Y., Niidome, T.. “Preparation of novel curcumin derivatives as βsecretase inhibitors”, PCT Int Appl, WO 2008066151 A1, 2008.
• [28] Ellman, G. L., Courtney, K. D., Andres Jr, V., Featherstone, R. M., “A new and rapid colorimetric determination of acetylcholinesterase activity”, Biochemical Pharmacology, 7, 88-95, 1961.
• [29] Hearing, V. J., Jiménez, M. Mammalian tyrosinase-the critical regulatory control point in melanocyte pigmentation. International Journal of Biochemistry, 19, 1141-1147, 1987.