請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/90693
標題: 3D quantitative structure-activity relationship studies of carbamates as inhibitors of acetylcholinesterase
作者: 張栢綸
Po-Lun Chang
關鍵字: acetylcholinesterase enzyme
carbamate inhibitors
引用: 1. 認識失智症。台灣失智症學會。http://www.tada2002.org.tw/tada_know_02.html 2. Richard L. Rotundo. Biogenesis of Acetylcholinesterase Molcular Forms in Muscle. Evidence for a rapidly turning over, catalytically inactive precursor pool. J. Biol. Chem. 1988, 263, 19398-19406. 3. Daniel E. Koshland, Jr. The Key-Lock Theory and the Induced Fit Theory. Angew. Chem. Int. Ed. Engl. 1994, 33, 2375-2378. 4. Jeremy M. Berg, John L. Tymoczko, Lubert Stryer. Biochemistry. Sixth Edition. Publication Date: April 1, 2011. Publisher: Palgrave MacMillan. 5. Types of Inhibition NIH Center for Translational Therapeutics. Retrieved 2 April 2012. http://en.wikipedia.org/wiki/Competitive_inhibition 6. Competitive Inhibition. Retrieved 2 April 2012. http://en.wikipedia.org/wiki/Competitive_inhibition 7. Enzyme Inhibitors. Virtual Chembook. Elmhurst college. Charles E Ophardt, c. 2003. http://en.wikipedia.org/wiki/Competitive_inhibition 8. Enzyme Inhibition Retrieved 2 April 2012. Clackamas Community College 2001, 2003 Clackamas Community College, Hal Bender http://en.wikipedia.org/wiki/Competitive_inhibition. 9. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003, 60, 1119-1122. 10. Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL. Neurochemical correlates of dementia severity in Alzheimer's disease: Relative importance of the cholinergic deficit. J. Neurochem. 1995, 64, 749-760. 11. Daniel M, Quinn. Acetylcholinesterase: Enzyme Structure, Reaction Dynamics, and Virtual Transition States. Chem. Rev. 1987, 87, 955-979. 12. Miyazawa A, Fujiyoshi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003, 423, 949-955. 13. http://www.proteopedia.org/wiki/index.php/Category:Acetylcholinesterase 14. Carletti E, Colletier JP, Dupeux F, Trovaslet M, Masson P, Nachon F. Structural Evidence That Human Acetylcholinesterase Inhibited by Tabun Ages through O-Dealkylation. J. Med. Chem. 2010, 53, 4002-4008. 15. Kryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL. Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta. Crystallogr. D. Biol. Crystallogr. 2000, 56, 1385-1394. 16. Ordentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, Shafferman A. Functional Characteristics of the Oxyanion Hole in Human Acetylcholinesterase. J. Biol. Chem. 1998, 273, 19509-19517. 17. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science, 1991, 253, 872-879. 18. Bourne Y, Taylor P, Radic Z, Marchot P. Structural insights into ligand interaction at the acetylcholinesterase peripheral anionic site. EMBO J. 2003, 22, 1-12. 19. Harel M, Kryger G, Rosenberry TL, Mallender WD, Lewis T, Fletcher RJ, Guss JM, Silman I, Sussman JL. Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors. Protein Sci. 2000, 6, 1063-1072. 20. Kryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL. Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta. Crystallogr. D. Biol. Crystallogr. 2000, 56, 1385-1394. 21. Taylor P. The Cholinesterases. J. Biol. Chem. 1991, 266, 4025-4028. 22. Taylor P, Radic Z. The Cholinesterases: From genes to Proteins. Annu. Rev. Pharmacol. Toxicol. 1994, 34, 281-320. 23. Davis KL, Charney D, Coyle JT, Nemeroff C. Current and Experimental Therapeutics of Alzheimer Disease. Neuropsychopharmacology. Publishers: Lippincott, Williams and Wilkins. 2002. 24. Karlsson E, Mbugua PM, Rodriguez-Ithurralde D. Fasciculins, anticholinesterase toxins from the venom of the green mamba Dendroaspis angusticeps. J. Physiol (Paris). 1984, 79, 232–240. 25. http://www.rcsb.org/pdb/101/motm.do?momID=54 26. Kryger G, Silman I, Sussman JL. Structure of acetylcholinesterase complexed with E2020 (Aricept R ): implications for the design of new anti-Alzheimer drugs. Structure. 1999, 7, 297–307. 27. 劉秀枝 翁文章 王署君, 阿茲海默症知能之藥物治療, 台北榮民總醫院精神醫學中心, 應用心理研究, 第 7 期, 2000 秋, 119-132 頁 28. Etienne P, Dastoor D, Gauthier S, Ludwick R, Collier B. Alzheimer's disease: lack of effect of lecithin treatment for 3 months. Neurology. 1981, 31, 1552-1554. 29. 阿茲海默氏症之藥物治療概論 黃詠銘藥師 花蓮慈濟醫院藥劑科。http://dlweb01.tzuchi.com.tw/dl/Med/joural/journal59.pdf。 30. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer's disease: a review of progress. J. Neurol. Neurosurg Psychiatry. 1999, 66, 137-147. 31. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA. 1994, 271, 992-998. 32. Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. U S A. 1993, 90, 9031-9035. 33. Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, Mohs RC, Thal LJ, Whitehouse PJ, DeKosky ST, Cummings JL. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001, 56, 1154-1166. 34. Bar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I. Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine. Biochemistry. 2002, 41, 3555-3564. 35. Greenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J. Am. Chem. Soc. 2004, 126, 15405-15411. 36. Gialih Lin, Hsin-Chang Tseng, Ai-Chi Chio, Tsao-Ming Tseng and Bo-Yi Tsai A rate determining step change in the pre-steady state of acetylcholinesterase inhibitions by ,n-alkane-di-N-butylcarbamates. Bioorg. Med. Chem. Lett. 15 (2005) 951–955 37. Gialih Lin, Cheng-Yue Lai and Wei-Cheng Liao. Molecular recognition by acetylcholinesterase at the peripheral anionic site: structure-activity relationships for inhibitions by aryl carbamates. Bioorg. Med. Chem. 7 (1999) 2683–2689 38. GIALIH LIN, YU-CHEN LIU, YAN-FU LIN and YON-GI WU. Ortho effects in quantitative structure-activity relationships for acetylcholinesterase inhibition by aryl carbamates. Journal of Enzyme Inhibition and Medicinal Chemistry, October 2004 Vol. 19 (5), pp. 395–401 39. Gialih Lin, Gan-Hong Chen, Shih-Chieh Yeh, and Chun-Ping Lu. Probing the peripheral anionic site of acetylcholinesterase with quantitative structure activity relationships for inhibition by biphenyl-4-acyoxylate-4′-N-Butylcarbamates. J BIOCHEM MOLECULAR TOXICOLOGY Volume 19, Number 4, 2005. 234-243 40. Gialih Lin, Cheng-Yue Lai , Wei-Chung Liao ,Pei-Shin Liao and Chung-Hwey Chan. Structure-Reactivity Relationships as Probes to Acetylcholinesterase Inhibition Mechanisms by Aryl Carbamates. I. Steady-State Kinetics. J. Chin. Chem. Soc., 2003, 50, 1259-1265 41. Perola E, Cellai L, Lamba D, Filocamo L, Brufani M. Long chain analogs of physostigmine as potential drugs for Alzheimer's disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase. Biochim. Biophys. Acta. 1997, 1343, 41-50. 42. Yu QS, Holloway HW, Greig NH, Brossi A. Total Syntheses and AnticholinesteraseActivitiesof(3aS)-N8 -Norphysostigmine, (3aS)-N8 -Norphenserine, their Antipodal Isomers, and Other N8 -Substituted Analogues. J. Med. Chem. 1997, 40, 2895-2901. 43. 王昭力。2008。 針對組蛋白去乙醯酵素抑制劑利用CoMFA、CoMSIA以及hQSAR分析三維和二維定量結構活性關係研究。國立彰化師範大學生物科技研究所碩士論文。 44. Kuan-Han Lee. Computer-Aided Drug Design in Drug Discovery. CHEMISTRY. 2003, 61, 655-670. 45. Wang, R., Gao, Y., Lai, L. LigBuilder: A Multi-Purpose Program for Structure-Based Drug Design. Journal of Molecular Modeling . (2000), 6 (7-8), 498–516. 46. Schneider, G., Fechner, U. Computer-based de novo design of drug-like molecules. Nat Rev Drug Discov .(2005),4 (8): 649–663. 47. Jorgensen, W. L. The many roles of computation in drug discovery. Science (2004), 303 (5665): 1813–1818. 48. 李仁利1998年藥物的構效關係北京大學藥學院講義 49. 陳凱先等2000年計算機輔助藥物設計——原理、方法及應用上海科學技術出版社ISBN 7-5323-5551-9 50. 徐筱傑等2004年計算機輔助藥物分子設計化學工業出版社ISBN 7-5025-5520-X 51. XIANG Yu-hong; XIAO Ai-jing; ZHANG Zhuo-yong, QSAR studies on a series of tetrahydroisoquinoline derivatives by using CoMFA, CoMSIA and HQSAR. Journal of Lanzhou University (Natural Sciences).2009, Vol. 45, No. 4 : 88-93 52. Shrikant S. Nilewar and Muthu K. Kathiravan, 3D CoMFA, CoMSIA, topomer CoMFA and HQSAR studies on aromatic acid esters for carbonic anhydrase inhibitory activity. J. Chemometrics (2013) 53. 莊祐仲。2007。利用三維定量結構活性關係之比較分子力場與比較分子類似指數分析一系列酪胺酸酶抑制劑的分子模擬研究。亞洲大學生物科技與生物資訊學研究所碩士論文。 54. Wang Wen-juan, Xiang Yu-hong, Song Jia, Zhang Zhuo-youg, Virtual screening and 3D-QSAR study based on acetylcholinesterase inhibitors of tacrine. Chemical research and application, 2014, Vol. 26, No. 2: 241-249 55. 陳桃菊。2009。酪胺酸激酶抑制劑的分子對接與三維定量構效關係的研究。中山大學化學與化學工程學院碩士論文。中華人民共和國。 56. Tenenhaus, M.; Esposito Vinzi, V.; Chatelinc, Y-M.; Lauro, C. (January 2005). 'PLS path modeling' (PDF). Computational Statistics & Data Analysis 48 (1): 159–205. doi:10.1016/j.csda.2004.03.005 57. Vinzi, V.; Chin, W.W.; Henseler, J. et al., eds. (2010). Handbook of Partial Least Squares. ISBN 978-3-540-32825-4. 58. 呂仁傑。2014。硫代胺基甲酸類與β-內醯胺酶和凝血酶分子對接研究。國立中興大學化學研究所碩士論文。
摘要: Acetylcholinesterase enzyme is the main topic of the treatment of Alzheimer's disease. In this study, I used a three-dimensional quantitative structure-activity relationship (3D QSAR) , to calculate the computer simulation models of 50 carbamate inhibitors inhibition constant (KI). The results presented a very high degree of similarity, and the R2 value results were all greater than 0.9, with statistical significance. Consequently, the results from the simulation of carbamate inhibitors presented that some long chains and phenyl F2 substituents got better inhibitory effect of the acetylcholinesterase enzyme. The results of this study provide a useful information in the future design of carbamate inhibitors, which could both save more time and reduce the costs it wasted.
乙醯膽鹼酯酵素(acetylcholinesterase enzyme)是治療阿茲海默症之主要標的物質,在本篇研究中,使用三維定量結構與活性關係(3D QSAR)計算,模擬50個氨基甲酸類抑制劑的抑制常數(KI)模型。其實驗結果呈現相當高度的相似度,且結果的R2值皆大於0.9,具統計學上之意義。透過對氨基甲酸類抑制劑模擬的分析結果,發現長鏈和苯的F2取代基對乙醯膽鹼酯酵素具有較佳的抑制效果。此研究結果可在未來設計氨基甲酸類抑制劑時,提供有效的資訊,以節省花費的時間與成本。
URI: http://hdl.handle.net/11455/90693
文章公開時間: 2016-01-23

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