نوع مقاله : مقاله پژوهشی
نویسندگان
1 گروه زیست‌شناسی، دانشگاه پیام نور، تهران، ایران
2 گروه فارماکوگنوزی و بیوتکنولوژی، دانشکده داروسازی، دانشگاه علوم پزشکی کرمانشاه، کرمانشاه، ایران
3 گروه شیمی دارویی، دانشکده داروسازی، دانشگاه علوم پزشکی تبریز، تبریز، ایران
10.30473/eab.2024.70624.1949
چکیده
آلزایمر از شایع‌ترین بیماری‌های تخریب‌کننده سیستم عصبی مرکزی است. پیشگیری و درمان این بیماری بسیار مهم است. یکی از اهداف درمانی برای بیماری آلزایمر مهار فعالیت آنزیم کولین‌استراز است. فلورتین و تریلوباتین از ترکیبات طبیعی پلی‌فنلی دی‌هیدروچالکونی هستند. تریلوباتین مشتق قندی فلورتین است. مطالعات نشان داده که این ترکیبات در یادگیری و حافظه مؤثر بوده و نیز خواص نوروپروتکتیوی دارند. در این مطالعه مهار فعالیت آنزیم بوتیریل کولین‌استراز توسط این ترکیبات بررسی شد. نتایج از لحاظ قدرت مهار و مکانیسم مولکولی برهم‌کنش برای هر ترکیب با آنزیم مقایسه شد. مهار فعالیت آنزیم توسط فلورتین و تریلوباتین به‌ترتیب 42 و 25 درصد بوده است. پیش‌بینی پارامترهای ADMET ترکیبات انجام شد. داکینگ مولکولی برای بررسی نحوه اتصال ترکیبات، نوع برهم‌کنش‌ها و محاسبه انرژی آزاد اتصال به‌کار رفت. طبق نتایج شبیه‌سازی داکینگ مولکولی، میانگین انرژی آزاد اتصال برای برهم‌کنش فلورتین و تریلوباتین با آنزیم به‌ترتیب (35/0±) 64/6- و (93/0±) 92/5- کیلوکالری/مول بود. گروه قندی در ساختار تریلوباتین باعث افزایش تعداد پیوندهای قابل چرخش، آب‌دوستی و ممانعت فضایی می‌شود. به‌نظر می‌رسد که این عوامل موجب کاهش قدرت مهاری تریلوباتین علیه آنزیم در مقایسه با فلورتین می‌شود. به‌طور کلی، براساس مطالعه حاضر این ترکیبات قدرت مهاری بالایی ندارند، اما با توجه به نتایج به‌دست‌آمده می‌توانند به‌عنوان ترکیبات پیشرو در طراحی داروهای جدید علیه آلزایمر و یا بخشی از مکمل‌های طبیعی ضد آلزایمر در نظر گرفته شوند.
کلیدواژه‌ها
موضوعات
Ademosun, A. O., Oboh, G., Bello, F., & Ayeni, P. O. (2016). Antioxidative properties and effect of quercetin and its glycosylated form (Rutin) on acetylcholinesterase and butyrylcholinesterase activities. Journal of evidence-based complementary & alternative medicine, 21(4), NP11-NP17.
Afkham, S., Hanaee, J., Zakariazadeh, M., Fathi, F., Shafiee, S., & Soltani, S. (2022). Molecular mechanism and thermodynamic study of Rosuvastatin interaction with human serum albumin using a surface plasmon resonance method combined with a multi-spectroscopic, and molecular modeling approach. European Journal of Pharmaceutical Sciences, 168, 106005.
Akhondzadeh, S., & Abbasi, S. H. (2006). Herbal medicine in the treatment of Alzheimer's disease. American Journal of Alzheimer's Disease & Other Dementias®, 21(2), 113-118.
Baghban, R., Ghasemali, S., Farajnia, S., Hoseinpoor, R., Andarzi, S., Zakariazadeh, M., & Zarredar, H. (2021). Design and in silico evaluation of a novel cyclic disulfide-rich anti-VEGF peptide as a potential antiangiogenic drug. International Journal of Peptide Research and Therapeutics, 27, 2245-2256.
Balkis, A., Tran, K., Lee, Y. Z., Balkis, K. N., & Ng, K. (2015). Screening flavonoids for inhibition of acetylcholinesterase identified baicalein as the most potent inhibitor. Journal of Agricultural Science, 7(9), 26.
Ballard, C., Gauthier, S., Corbett, A., Brayne, C., Aarsland, D., & Jones, E. (2011). Alzheimer's disease. the Lancet, 377(9770), 1019-1031.
Ballard, C. G., Greig, N. H., Guillozet-Bongaarts, A. L., Enz, A., & Darvesh, S. (2005). Cholinesterases: roles in the brain during health and disease. Current Alzheimer Research, 2(3), 307-318.
Barreca, D., Currò, M., Bellocco, E., Ficarra, S., Laganà, G., Tellone, E., Galtieri, A., & Lentile, R. (2017). Neuroprotective effects of phloretin and its glycosylated derivative on rotenone‐induced toxicity in human SH‐SY5Y neuronal‐like cells. Biofactors, 43(4), 549-557.
Blaikie, L., Kay, G., & Lin, P. K. T. (2019). Current and emerging therapeutic targets of alzheimer's disease for the design of multi-target directed ligands. MedChemComm, 10(12), 2052-2072.
Breijyeh, Z., & Karaman, R. (2020). Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 25(24), 5789.
Cao, J., Hou, J., Ping, J., & Cai, D. (2018). Advances in developing novel therapeutic strategies for Alzheimer’s disease. Molecular neurodegeneration, 13, 1-20.
Chen, N., Wang, J., He, Y., Xu, Y., Zhang, Y., Gong, Q., & Gao, J. (2020). Trilobatin protects against Aβ25–35-induced hippocampal HT22 cells apoptosis through mediating ROS/p38/Caspase 3-dependent pathway. Frontiers in pharmacology, 11, 584.
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020). Alzheimer's disease drug development pipeline: 2020. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 6(1), e12050.
Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer's research & therapy, 6(4), 1-7.
Dangles, O. (2012). Antioxidant activity of plant phenols: chemical mechanisms and biological significance. Current Organic Chemistry, 16(6), 692-714.
De Luca, F., Di Chio, C., Zappalà, M., & Ettari, R. (2022). Dihydrochalcones as Antitumor Agents. Current Medicinal Chemistry, 29(30), 5042-5061.
de Oliveira, M.R. (2016). Phloretin‐induced cytoprotective effects on mammalian cells: A mechanistic view and future directions. Biofactors, 42(1), 13-40.
DeLano, W.L. (2002). Pymol: An open-source molecular graphics tool. CCP4 Newsl. Protein Crystallogr, 40(1), 82-92.
Didziapetris, R., Japertas, P., Avdeef, A., & Petrauskas, A. (2003). Classification analysis of P-glycoprotein substrate specificity. Journal of drug targeting, 11(7), 391-406.
Dwivedi, S., Malik, C., & Chhokar, V. (2017). Molecular structure, biological functions, and metabolic regulation of flavonoids. Plant Biotechnology: Recent Advancements and Developments, 171-188.
Farrokhi, H., Mozaffarnia, S., Rahimpour, K., Rashidi, M. R., & Teimuri-Mofrad, R. (2020). Synthesis, characterization and investigation of AChE and BuChE inhibitory activity of 1-alkyl-4-[(5, 6-dimethoxy-1-indanone-2-yl) methylene] pyridinium halide derivatives. Journal of the Iranian Chemical Society, 17, 593-600.
Farsad, S. A., Haghaei, H., Shaban, M., Zakariazadeh, M., & Soltani, S. (2022). Investigations of the molecular mechanism of diltiazem binding to human serum albumin in the presence of metal ions, glucose and urea. Journal of Biomolecular Structure and Dynamics, 40(15), 6868-6879.
Ferreira, L. L., & Andricopulo, A. D. (2019). ADMET modeling approaches in drug discovery. Drug discovery today, 24(5), 1157-1165.
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999). The cholinergic hypothesis of Alzheimer’s disease: a review of progress. Journal of Neurology, Neurosurgery & Psychiatry, 66(2), 137-147.
Gao, J., Liu, S., Xu, F., Liu, Y., Lv, C., Deng, Y., Shi, J., & Gong, Q. (2018). Trilobatin protects against oxidative injury in neuronal PC12 cells through regulating mitochondrial ROS homeostasis mediated by AMPK/Nrf2/Sirt3 signaling pathway. Frontiers in Molecular Neuroscience, 11, 267.
Ghose, A. K., Viswanadhan, V. N., & Wendoloski, J. J. (1999). A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. Journal of combinatorial chemistry, 1(1), 55-68.
Ghumatkar, P. J., Patil, S. P., Jain, P. D., Tambe, R. M., & Sathaye, S. (2015). Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice. Pharmacology Biochemistry and Behavior, 135, 182-191.
Giacobini, E. (2001). Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer’s disease? Drugs & aging, 18, 891-898.
Gorun, V., Proinov, I., Băltescu, V., Balaban, G., & Bârzu, O. (1978). Modified Ellman procedure for assay of cholinesterases in crude enzymatic preparations. Analytical biochemistry, 86(1), 324-326.
Govindarajulu, M., Ramesh, S., Neel, L., Fabbrini, M., Buabeid, M., Fujihashi, A., Mohanakumar, K. P. ...& Dhanasekaran, M. (2021). Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease. Neurochemistry international, 144, 104958.
Guengerich, F. P. (1997). Role of cytochrome P450 enzymes in drug-drug interactions. Advances in pharmacology, 43, 7-35.
Gürsoy, O., & Smieško, M. (2017). Searching for bioactive conformations of drug-like ligands with current force fields: how good are we? Journal of Cheminformatics, 9, 1-13.
Hodgson, J. (2001). ADMET—turning chemicals into drugs. Nature biotechnology, 19(8), 722-726.
Ibdah, M., Martens, S., & Gang, D. R. (2017). Biosynthetic pathway and metabolic engineering of plant dihydrochalcones. Journal of agricultural and food chemistry, 66(10), 2273-2280.
Işık, M., & Beydemir, Ş. (2021). The impact of some phenolic compounds on serum acetylcholinesterase: kinetic analysis of an enzyme/inhibitor interaction and molecular docking study. Journal of Biomolecular Structure and Dynamics, 39(17), 6515-6523.
Kalyaanamoorthy, S., & Barakat, K. H. (2018). Development of safe drugs: the hERG challenge. Medicinal Research Reviews, 38(2), 525-555.
Kamdi, S. P., Badwaik, H. R., Raval, A., & Nakhate, K. T. (2021). Ameliorative potential of phloridzin in type 2 diabetes-induced memory deficits in rats. European Journal of Pharmacology, 913, 174645.
Karami, K., Ramezanpour, A., Zakariazadeh, M., Shahpiri, A., Kharaziha, M., & Kazeminasab, A. (2019). Luminescent Palladacycles Containing a Pyrene Chromophor; Synthesis, Biological and Computational Studies of the Interaction with DNA and BSA. ChemistrySelect, 4(17), 5126-5137.
Karimi, G., Iranshahi, M., Hosseinalizadeh, F., Riahi, B., & Sahebkar, A. (2010). Screening of acetylcholinesterase inhibitory activity of terpenoid and coumarin derivatives from the genus Ferula. Pharmacologyonline, 1, 566-574.
Katalinić, M., Rusak, G., Barović, J. D., Šinko, G., Jelić, D., Antolović, R., & Kovarik, Z. (2010). Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. European Journal of Medicinal Chemistry, 45(1), 186-192.
Khandan Alamdari, S., Farahmand, S., Haji Hosseini, R., & Bakhshi khaniki, G. (2023). Computational design of E6 protein inhibitors for the treatment of HPV16 disease. Experimental animal Biology, 12(2), 1-14. https://doi.org/10.30473/eab.2023.68784.1920
Kuehne, A., Floerl, S., & Hagos, Y. (2022). Investigations with drugs and pesticides revealed new species-and substrate-dependent inhibition by Elacridar and Imazalil in human and mouse organic cation transporter OCT2. International journal of molecular sciences, 23(24), 15795.
Kumar, A., & Dogra, S. (2008). Neuropathology and therapeutic management of Alzheimer's disease--An update. Drugs of the Future, 33(5), 433-446.
Kumar, A., & Singh, A. (2015). A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacological reports, 67(2), 195-203.
Łapczuk-Romańska, J., Droździk, M., Oswald, S., & Droździk, M. (2023). Kidney Drug Transporters in Pharmacotherapy. International journal of molecular sciences, 24(3), 2856.
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 23(1-3), 3-25.
Long, S., Benoist, C., & Weidner, W. (2023). World Alzheimer report 2023. Reducing dementia risk: never too early, never too late. Alzheimer’s Disease International (ADI): London, UK, 7.
Ma, X.-l., Chen, C., & Yang, J. (2005). Predictive model of blood-brain barrier penetration of organic compounds. Acta Pharmacologica Sinica, 26(4), 500-512.
Manikandan, P., & Nagini, S. (2018). Cytochrome P450 structure, function and clinical significance: a review. Current drug targets, 19(1), 38-54.
Mansouri, A., Kowsar, R., Zakariazadeh, M., Hakimi, H., & Miyamoto, A. (2022). The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: A molecular modeling approach. Scientific Reports, 12(1), 717.
Massoulié, J., Sussman, J., Bon, S., & Silman, I. (1993). Structure and functions of acetylcholinesterase and butyrylcholinesterase. Progress in brain research, 98, 139-146.
Mozaffarnia, S., Parsaee, F., Payami, E., Karami, H., Soltani, S., Rashidi, M. R., & Teimuri‐Mofrad, R. (2019). Design, Synthesis and Biological Assessment of Novel 2‐(4‐Alkoxybenzylidine)‐2, 3‐dihydro‐5, 6‐dimethoxy‐1H‐inden‐1‐one Derivatives as hAChE and hBuChE Enzyme Inhibitors. ChemistrySelect, 4(32), 9376-9380.
Mozaffarnia, S., Teimuri-Mofrad, R., & Rashidi, M.-R. (2020). Design, synthesis and biological evaluation of 2, 3-dihydro-5, 6-dimethoxy-1H-inden-1-one and piperazinium salt hybrid derivatives as hAChE and hBuChE enzyme inhibitors. European Journal of Medicinal Chemistry, 191, 112140.
Nordberg, A., Ballard, C., Bullock, R., Darreh-Shori, T., & Somogyi, M. (2013). A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer's disease. The primary care companion for CNS disorders, 15(2), 26731.
Pantaleão, S. Q., Fernandes, P. O., Gonçalves, J. E., Maltarollo, V. G., & Honorio, K. M. (2022). Recent advances in the prediction of pharmacokinetics properties in drug design studies: a review. ChemMedChem, 17(1), e202100542.
Rudrapal, M., Khan, J., Dukhyil, A. A. B., Alarousy, R. M. I. I., Attah, E. I., Sharma, T.,…& Bendale, A. R. (2021). Chalcone scaffolds, bioprecursors of flavonoids: Chemistry, bioactivities, and pharmacokinetics. Molecules, 26(23), 7177.
Schmidt, S., Gonzalez, D., & Derendorf, H. (2010). Significance of protein binding in pharmacokinetics and pharmacodynamics. Journal of pharmaceutical sciences, 99(3), 1107-1122.
Self, W. K., & Holtzman, D. M. (2023). Emerging diagnostics and therapeutics for Alzheimer disease. Nature Medicine, 1-13.
Shallangwa, G. A., & Adeniji, S. E. (2021). Binding profile of protein–ligand inhibitor complex and structure based design of new potent compounds via computer-aided virtual screening. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 24, 100256.
Shang, A., Liu, H.-Y., Luo, M., Xia, Y., Yang, X., Li, H.-Y.,…& Gan, R.-Y. (2022). Sweet tea (Lithocarpus polystachyus rehd.) as a new natural source of bioactive dihydrochalcones with multiple health benefits. Critical Reviews in Food Science and Nutrition, 62(4), 917-934.
Singh, S., & Singh, J. (1993). Transdermal drug delivery by passive diffusion and iontophoresis: a review. Medicinal Research Reviews, 13(5), 569-621.
Slámová, K., Kapešová, J., & Valentová, K. (2018). Sweet flavonoids: Glycosidase-catalyzed modifications. International journal of molecular sciences, 19(7), 2126.
Srivastava, S., Ahmad, R., & Khare, S. K. (2021). Alzheimer’s disease and its treatment by different approaches: A review. European Journal of Medicinal Chemistry, 216, 113320.
Stanciu, G.D., Luca, A., Rusu, R.N., Bild, V., Beschea Chiriac, S.I., Solcan, C.,…& Ababei, D. C. (2019). Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules, 10(1), 40.
Sun, M., Su, M., & Sun, H. (2018). Spectroscopic investigation on the interaction characteristics and inhibitory activities between baicalin and acetylcholinesterase. Medicinal Chemistry Research, 27(6), 1589-1598.
Szwajgier, D. (2013). Anticholinesterase activity of phenolic acids and their derivatives. Zeitschrift für Naturforschung C, 68(3-4), 125-132.
Szwajgier, D. (2014). Anticholinesterase activities of selected polyphenols–a short report. Polish Journal of Food and Nutrition Sciences, 64(1), 59-64.
Teague, S. J., Davis, A. M., Leeson, P. D., & Oprea, T. (1999). The design of leadlike combinatorial libraries. Angewandte Chemie International Edition, 38(24), 3743-3748.
Tomassini, L., Ventrone, A., Frezza, C., Fabbri, A. M., Fortuna, S., Volpe, M. T., & Cometa, M. F. (2021). Phytochemical analysis of Viburnum davidii Franch. and cholinesterase inhibitory activity of its dihydrochalcones. Natural Product Research, 35(24), 5794-5800.
Trifan, A., & Luca, S. V. (2023). Phloretin: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology. In J. Xiao (Ed.), Handbook of Dietary Flavonoids (pp. 1-31). Springer International Publishing. https://doi.org/10.1007/978-3-030-94753-8_26-1
Veiga-Matos, J., Morales, A. I., Prieto, M., Remião, F., & Silva, R. (2023). Study Models of Drug–Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels. Molecules, 28(22), 7532.
Viet, M. H., Chen, C.-Y., Hu, C.-K., Chen, Y.-R., & Li, M. S. (2013). Discovery of dihydrochalcone as potential lead for Alzheimer’s disease: in silico and in vitro study. PloS one, 8(11), e79151.
Vrbanac, J., & Slauter, R. (2017). ADME in drug discovery. In A comprehensive guide to toxicology in nonclinical drug development (pp. 39-67). Elsevier.
Wu, D., Chen, Q., Chen, X., Han, F., Chen, Z., & Wang, Y. (2023). The blood–brain barrier: structure, regulation, and drug delivery. Signal transduction and targeted therapy, 8(1), 217.
Xie, Y., Yang, W., Chen, X., & Xiao, J. (2014). Inhibition of flavonoids on acetylcholine esterase: binding and structure–activity relationship. Food & Function, 5(10), 2582-2589.
Yazdanian, M., Glynn, S. L., Wright, J. L., & Hawi, A. (1998). Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharmaceutical research, 15(9), 1490.
Yee, S. (1997). In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man—fact or myth. Pharmaceutical research, 14, 763-766.
Yin, J., & Wang, J. (2016). Renal drug transporters and their significance in drug–drug interactions. Acta Pharmaceutica Sinica B, 6(5), 363-373.
Yu, S., He, M., Zhai, Y., Xie, Z., Xu, S., Yu, S.,…& Song, Y. (2021). Inhibitory activity and mechanism of trilobatin on tyrosinase: kinetics, interaction mechanism and molecular docking. Food & Function, 12(6), 2569-2579.
Yu, X.-Q., & Wilson, A. G. (2010). The role of pharmacokinetic and pharmacokinetic/ pharmacodynamic modeling in drug discovery and development. Future Medicinal Chemistry, 2(6), 923-928.
Zakariazadeh, M., Barzegar, A., Soltani, S., & Aryapour, H. (2015). Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity. Medicinal Chemistry Research, 24, 2485-2504.
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X.,…He, L., & Qin, S. (2021). Cytochrome P450 enzymes and drug metabolism in humans. International journal of molecular sciences, 2, 2(23), 12808.
Zhong, H., Hao, L., Li, X., Wang, C., & Wu, X. (2020). Anti-inflammatory Role of Trilobatin on Lipopolysaccharide-induced Acute Lung Injury through Activation of AMPK/GSK3β-Nrf2 Pathway. Signa Vitae, 16(2), 160.
Zuo, A.-R., Yu, Y.-Y., Shu, Q.-L., Zheng, L.-X., Wang, X.-M., Peng, S.-H., … & Cao, S.-W. (2014). Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone. Journal of the Chinese Medical Association, 77(6), 290-301.
)