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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張嘉銓 | zh_TW |
| dc.contributor.advisor | Chia-Chuan Chang | en |
| dc.contributor.author | 羅暐智 | zh_TW |
| dc.contributor.author | Wei-Chih Lo | en |
| dc.date.accessioned | 2021-05-19T17:47:57Z | - |
| dc.date.available | 2023-12-13 | - |
| dc.date.copyright | 2018-03-29 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Hurley, T. D.; Edenberg, H. J.; Li, T. K., Pharmacogenomics of alcoholism. In Pharmacogenomics: The Search for Individualized Therapies [online]; John Wiley & Sons: New York, 2003; Chapter 21, pp 417-441. http://onlinelibrary.wiley.com/doi/10.1002/3527600752.ch21/summary (accessed Aug 16, 2017)
2. Chen, C. H.; Ferreira, J. C. B.; Gross, E. R.; Mochly-Rosen, D., Targeting aldehyde dehydrogenase 2: New therapeutic opportunities. Physiol. Rev. 2014, 94 (1), 1-34. 3. Larson, H. N.; Weiner, H.; Hurley, T. D., Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase ‘asian’ variant. J. Biol. Chem. 2005, 280 (34), 30550-6. 4. Steinmetz, C. G.; Xie, P.; Weiner, H.; Hurley, T. D., Structure of mitochondrial aldehyde dehydrogenase: The genetic component of ethanol aversion. Structure 1997, 5 (5), 701-711. 5. Koppaka, V.; Thompson, D. C.; Chen, Y.; Ellermann, M.; Nicolaou, K. C.; Juvonen, R. O.; Petersen, D.; Deitrich, R. A.; Hurley, T. D.; Vasiliou, V., Aldehyde dehydrogenase inhibitors: A comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol. Rev. 2012, 64 (3), 520-39. 6. Perez-Miller, S. J.; Hurley, T. D., Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase. Biochemistry 2003, 42 (23), 7100-7109. 7. Larson, H. N.; Zhou, J.; Chen, Z.; Stamler, J. S.; Weiner, H.; Hurley, T. D., Structural and functional consequences of coenzyme binding to the inactive asian variant of mitochondrial aldehyde dehydrogenase: roles of residues 475 and 487. J. Biol. Chem. 2007, 282 (17), 12940-50. 8. Chen, C.-H.; Budas, G. R.; Churchill, E. N.; Disatnik, M.-H.; Hurley, T. D.; Mochly-Rosen, D., Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart. Science 2008, 321 (5895), 1493-1495. 9. Perez-Miller, S.; Younus, H.; Vanam, R.; Chen, C. H.; Mochly-Rosen, D.; Hurley, T. D., Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat. Struct. Mol. Biol. 2010, 17 (2), 159-164. 10. 臺灣藥學會生藥學組，常用中藥。臺灣藥學會：臺北，2012年；第133頁。 11. Choi, Y. Y.; Kim, M. H.; Han, J. M.; Hong, J.; Lee, T. H.; Kim, S. H.; Yang, W. M., The anti-inflammatory potential of Cortex Phellodendron in vivo and in vitro: Down-regulation of NO and iNOS through suppression of NF-κB and MAPK activation. Int. Immunopharmacol. 2014, 19 (2), 214-220. 12. Chen, M. L.; Xian, Y. F.; Ip, S. P.; Tsai, S. H.; Yang, J. Y.; Che, C. T., Chemical and biological differentiation of Cortex Phellodendri Chinensis and Cortex Phellodendri Amurensis. Planta Med. 2010, 76 (14), 1530-5. 13. 姜玉龍。國立成功大學化學研究所碩士論文：臺灣黃柏根部之成分研究。2005年。 14. Cheng, Z.; Chen, A. F.; Wu, F.; Sheng, L.; Zhang, H. K.; Gu, M.; Li, Y. Y.; Zhang, L. N.; Hu, L. H.; Li, J. Y.; Li, J., 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Biorg. Med. Chem. 2010, 18 (16), 5915-5924. 15. Koszyk, F. J.; Lenz, G. R., Lead tetraacetate oxidation of oxyprotoberberines. A convenient synthesis of 13-oxygenated berbines and oxyprotoberberines. J. Org. Chem. 1984, 49 (14), 2642-2644. 16. Hanaoka, M.; Mukai, C.; Arata, Y., Chemical Transformation of Protoberberines. III. Convenient Synthesis of 8-Methoxyberberinephenolbetaine by Photooxygenation of Berberine. A Novel Conversion of Berberine into (±)-Ophiocarpine, (±)-Epiophiocarpine, (±)-a-Hydrastine, and (±)-b-Hydrastine. Chem. Pharm. Bull. (Tokyo) 1983, 31 (3), 947-952. 17. Valeur, E.; Bradley, M., Amide bond formation: beyond the myth of coupling reagents. Chem. Soc. Rev. 2009, 38 (2), 606-631. 18. Beretta, M.; Gorren, A. C. F.; Wenzl, M. V.; Weis, R.; Russwurm, M.; Koesling, D.; Schmidt, K.; Mayer, B., Characterization of the East Asian Variant of Aldehyde Dehydrogenase-2: BIOACTIVATION OF NITROGLYCERIN AND EFFECTS OF Alda-1. J. Biol. Chem 2010, 285 (2), 943-952. 19. Moniot, J. L.; Shamma, M., Conversion of berberine into phthalideisoquinolines. J. Org. Chem. 1979, 44 (24), 4337-4342. 20. Masahiko, S. Process for production of biphenyl derivative. US Patent 2012232283, Sep 13, 2012. 21. Allen, C. L.; Davulcu, S.; Williams, J. M. J., Catalytic Acylation of Amines with Aldehydes or Aldoximes. Org. Lett. 2010, 12 (22), 5096-5099. 22. Lee, S. S.; Dung, K. T., Semisynthesis of tetrahydropalmatine, an active ingredient from Corydalis Balbosa, from berberine. Chin. Pharm. J. 1991, 43 (4), 303-309. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7615 | - |
| dc.description.abstract | 粒線體醛去氫酶2 (mitochondrial aldehyde dehydrogenase 2, ALDH2)為人體乙醇代謝途徑上重要的酵素之一。約5.6億東亞人(佔世界人口8%)有不具活性之ALDH2*2對偶基因。近幾年的研究指出，此喪失活性之突變，除了使個體較容易被內生性或外源性醛類損害，也可能與心血管疾病、糖尿病、上呼吸消化道癌症等有關。粒線體醛去氫酶2活化劑最早於2008年以高通量篩選的方式篩選出來，其中以Alda-1具有最好的粒線體醛去氫酶2促進活性。
本實驗根據Alda-1之結構，製備出一系列類似物。以EDC偶合的方式，將piperonylamine與一系列的苯甲酸，或是piperonylic acid與一系列苯甲胺進行醯胺偶合反應，得到化合物3a–h及6a–e。考量到人為設計化合物時，常一味追求更強之結合親和力(binding affinity)而忽略其毒性，所以除了合成Alda-1類似物之外，本實驗以小檗鹼為起始物，製備得到存在於臺灣黃柏根部之微量成分：methyl anhydroberberilate，其具有與Alda-1相似之N-piperonylbenzamide結構。而後藉由野生型粒線體醛去氫酶2活性促進試驗，觀察結構上的改變對促進活性有何影響。 結構-活性關係之探討發現羰基之位置對於促進活性可能有重要影響：當羰基位於甲苯基團之苄基位時(即化合物3b–h)，促進活性較羰基位於3,4-亞甲二氧苄基團之苄基位，最多增強約51倍。由電腦分子模擬結果推測影響活性之關鍵因素為「羰基位於甲苯基團或3,4-亞甲二氧苄基團之苄基位時，化合物之醯胺基氫與Asp457主鏈羰基是否在可產生氫鍵之距離內」。其次，苯甲醯基2'或6'位置至少須存在一個取代基，使Alda-1類似物能與野生型粒線體醛去氫酶2以正確的方式作用，例如：化合物3a苯甲醯基2'或6'位置無任何取代基，不同於其它Alda-1類似物以3,4-亞甲二氧苄基團插入野生型粒線體醛去氫酶2受質出入口，而是以苯甲醯基芳香環插入酵素受質出入口，使其醯胺基氫與Asp457主鏈羰基之距離大於氫鍵可作用距離。此外，若2'或6'位置上之取代基使苯甲醯基之芳香環較為疏水性，其與酵素受質出入口許多疏水性胺基酸會有較佳之疏水性作用力，且其造成之立體障礙越小越好。最後，3,4-亞甲二氧苄基基團之苯環須與Phe459支鏈芳香環平行以得到較佳之π-πi交互作用。 | zh_TW |
| dc.description.abstract | ALDH2 is one of the most important enzymes in ethanol metabolism. There are around 560 million East Asians (nearly 8% of the world’s population) carrying the inactive ALDH2*2 allel. Recent studies indicated that ALDH2*2 would not protect individuals from the damages caused by endogenous or exogenous aldehydes, and it may relate to cardiovascular diseases and upper aerodigestive track cancers, etc. The earliest ALDH2 activators are discovered by high-throughput screening in 2008. Among these ALDH2 activators, Alda-1 has the best activating effects.
A series of Alda-1 analogs were prepared in the study. Compounds 3a–h and 6a–e were prepared from coupling piperonylamine or piperonylic acid with a series of benzoic acid or benzylamine by EDC. Considering compounds are often designed to pursue higher binding affinity but ignoring the toxicity, a minor constituent (methyl anhydroberberilate) in the roots of Phellodendron amurense var. wilsonii, which is similar to the N-piperonylbenzamide structure of Alda-1, was prepared from berberine. Through the wild-type ALDH2 activation assay, the structural impact on the activating ability was disclosed. Investigation on the structure-activity relationship suggested that the position of carbonyl group in these compounds might play the most important role in activating wild-type ALDH2: when carbonyl groups were located at the benzylic position of benzyl group of these compounds (3b–h), the activating abilities were better than those which carbonyl groups were located at the benzylic position of piperonyl group up to 51-fold. The computational molecular modeling results point out the most important role in activating wild-type ALDH2 is the capability of forming hydrogen bonds between amide hydrogen of the compounds and the main chain carbonyl group of Asp457 of the wild-type ALDH2. Secondly, there must exist at least one substitution group on either 2' or 6' position on the benzoyl group to make the Alda-1 analogs interact with wild-type ALDH2 correctly; e.g., there are not any substitution group at the 2' or 6' position on the benzoyl group of compound 3a, and it inserts into the substrate exit of wild-type ALDH2 by the benzoyl group instead of piperonyl group which makes the distance between amide hydrogen of 3a and the main chain carbonyl group of Asp457 beyond the hydrogen-bondable distance. In addition, if the 2' or 6' substitution groups make the aromatic ring of benzoyl group more hydrophobic, it would have better hydrophobic interaction with the many hydrophobic amino acids around the substrate exit of the enzyme. Moreover, the smaller steric interactions caused by the 2' or 6' substitution groups, the better the activity achieved. Finally, the aromatic ring of piperonyl group should be parallel to the aromatic side chain of Phe459 to get a proper π-π interaction. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-19T17:47:57Z (GMT). No. of bitstreams: 1 ntu-107-R04423030-1.pdf: 6076191 bytes, checksum: c8596d5542c91560912faa44233b93ad (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 總目錄（Contents）
中文摘要 I Abstract III 總目錄（Contents） V 圖目錄（List of figures） VII 表目錄（List of table） VIII 流程圖目錄（List of schemes） VIII 附圖目錄（List of supporting figures） IX 1. 緒論 1 1.1. 粒線體醛去氫酶2 (mitochondrial aldehyde dehydrogenase 2, ALDH2) 1 1.2. 野生型及亞洲變異型粒線體醛去氫酶2 7 1.3. 粒線體醛去氫酶2活化劑 10 1.4. Methyl anhydroberberilate 13 1.5. 研究目的 13 2. 結果與討論 14 2.1. Alda-1 analogs-1 (3a–h)與analogs-2 (6a–e)之製備 14 2.2. Methyl anhydroberberilate (10)之製備 23 2.3. 體外野生型粒線體醛去氫酶2促進活性結果 26 3. 實驗方法 32 3.1. 儀器與材料 32 3.1.1. 理化性質測定儀器 32 3.1.2. cLogP預測軟體 32 3.1.3. 電腦分子模擬計算軟體 32 3.1.4. 分子模擬結果成像軟體 32 3.1.5. 化合物核磁共振圖譜預測 33 3.1.6. 化合物合成、純化使用之材料、溶劑與試藥 33 3.1.6.1. 化合物純化所使用之材料 33 3.1.6.2. 溶劑 33 3.1.6.3. 試藥 33 3.1.7. 粒線體醛去氫酶2促進活性試驗所用試劑與儀器 35 3.2. 化合物之製備 36 3.2.1. Alda-1 analogs-1 (3a–h)之製備 36 3.2.2. Alda-1 analogs-2 (6a–e)之製備 45 3.2.3. Methyl anhydroberberilate (10)之製備 51 3.2.3.1. Oxyberberine (8)之製備 51 3.2.3.2. 13-Acetoxyoxoberberine (9)之製備 52 3.2.3.3. Methyl anhydroberberilate (10)之製備 53 3.3. 粒線體醛去氫酶2促進活性試驗 54 3.3.1. 原理 54 3.3.2. 實驗方法 54 3.3.2.1. 試劑配製 54 3.3.2.2. 實驗步驟 55 參考文獻 57 圖目錄（List of figures） Figure 1. 粒線體醛去氫酶2示意圖 2 Figure 2. 粒線體醛去氫酶2之單體及其部分二級結構 2 Figure 3. 粒線體醛去氫酶2四級結構 3 Figure 4. 介面示意圖 3 Figure 5. The metabolic mechanism of ALDH2 4 Figure 6. Nicotinamide adenine dinucleotide 5 Figure 7. Interactions of the cofactor with surrounding residues 6 Figure 8. Close contacts made by the nicotinamide ribose and ring 6 Figure 9. Stereoviews of cofactor binding 8 Figure 10. An alignment of ALDH2*2 subunits A and B to wild-type ALDH2 9 Figure 11. ALDH2與Alda-1、daidzin之結晶結構重疊 11 Figure 12. Alda-1促進ALDH2之可能機轉 11 Figure 13. (A) wild-type ALDH2結晶結構 (B) ALDH2*2結晶結構 (C) ALDH2*2與Alda-1共結晶結構 12 Figure 14. 以ChemBio 3D計算化合物9之能量最小立體結構 24 Figure 15. Activation (%) of ALDH2 by compounds 3a–h、6a–e及10 26 Figure 16. 化合物3h及6e與野生型粒線體醛去氫酶2鍵結之電腦分子模擬結果 28 Figure 17. 化合物3a與野生型粒線體醛去氫酶2鍵結之電腦分子模擬結果 28 Figure 18. 化合物3a與野生型粒線體醛去氫酶2鍵結之另一種電腦分子模擬結果 29 Figure 19. 化合物3e與野生型粒線體醛去氫酶2鍵結之電腦分子模擬結果 30 Figure 20. 化合物3f與野生型粒線體醛去氫酶2鍵結之電腦分子模擬結果 30 Figure 21. 影響Alda analogs促進活性之可能基團(紅色部分) 31 Figure 21. 96孔微量測試盤樣品添加方式 55 表目錄（List of table） Table 1. 1H (400 MHz) and 13C (50 MHz) NMR data of 3a–c in CDCl3 17 Table 2. 1H (400 MHz) and 13C (50 MHz) NMR data of 3d, 3g in CDCl3 18 Table 3. 1H (400 MHz) and 13C (BBD, 50 MHz) NMR data of 3e and 3f in CDCl3 19 Table 4. 1H, 13C NMR, HSQC and HMBC data of 3h in CD3OD (600 MHz) 20 Table 5. 1H (400 MHz) or 13C (50 MHz) NMR data of 6a, 6b and 6e in CD3OD or CDCl3, respectively 21 Table 6. 1H (400 MHz) or 13C (BBD, 50 MHz) NMR data of 6c and 6d in CD3OD or CDCl3, respectively 22 Table 7. 化合物3a–h、6a–e及10於15 g/mL與莫耳濃度之換算表 26 Table 8. 化合物3a–h、6a–e及10之分子量、clog P、氫鍵給予者數量與氫鍵接受者數量 27 流程圖目錄（List of schemes） Scheme 1. Preparation of compounds 3a–h 14 Scheme 2. Preparation of compounds 6a–e 14 Scheme 3. Amide generation by EDC coupling reaction 15 Scheme 4. Preparation of Alda-1 by addition-elimination of 2,6-dichlorobenzoyl chloride and piperonylamine1 15 Scheme 5. Preparation of methyl anhydroberberilate (10) 23 Scheme 6. Proposed mechanism of the C ring opening of 9 25 附圖目錄（List of supporting figures） Figure S1. 1H NMR spectrum of 3a (CDCl3, 400 MHz) 60 Figure S2. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3a (CDCl3, 50 MHz) 61 Figure S3. 1H NMR spectrum of 3b (CDCl3, 400 MHz) 62 Figure S4. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3b (CDCl3, 50 MHz) 63 Figure S5. 1H NMR spectrum of 3c (CDCl3, 400 MHz) 64 Figure S6. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3c (CDCl3, 50 MHz) 65 Figure S7. 1H NMR spectrum of 3d (CDCl3, 400 MHz) 66 Figure S8. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bot) of 3d (CDCl3, 50 MHz) 67 Figure S9. 1H NMR spectrum of 3e (CDCl3, 400 MHz) 68 Figure S10. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3e (CDCl3, 50 MHz) 69 Figure S11. 1H NMR spectrum of 3f (CDCl3, 400 MHz) 70 Figure S12. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3f (CDCl3, 50 MHz) 71 Figure S13. 1H NMR spectrum of 3g (CDCl3, 400 MHz) 72 Figure S14. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3g (CDCl3, 50 MHz) 73 Figure S15. 1H NMR spectrum of 3h (CDCl3, 400 MHz) 74 Figure S16. 1H NMR spectrum of 3h (CD3OD, 400 MHz) 75 Figure S17. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 3h (CDCl3, 100 MHz) 76 Figure S18. 1H NMR spectrum of 3h (CD3OD, 600 MHz), top; 13C NMR spectrum (BBD) of 3h (CD3OD, 150 MHz), bot. 77 Figure S19. HSQC spectrum of 3h (CD3OD, 600 MHz) (I) 78 Figure S20. HSQC spectrum of 3h (CD3OD, 600 MHz) (II) 79 Figure S21. HMBC spectrum of 3h (CD3OD, 600 MHz) (I) 80 Figure S22. HMBC spectrum of 3h (CD3OD, 600 MHz) (II) 81 Figure S23. HMBC spectrum of 3h (CD3OD, 600 MHz) (III) 82 Figure S24. 1H NMR spectrum of 6a (CDCl3, 200 MHz) 83 Figure S25. 1H NMR spectrum of 6a (CD3OD, 400 MHz) 84 Figure S26. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 6a (CDCl3, 50 MHz) 85 Figure S27. 1H NMR spectrum of 6b (CDCl3, 400 MHz) 86 Figure S28. 1H NMR spectrum of 6b (CD3OD, 400 MHz) 87 Figure S29. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 6b (CDCl3, 50 MHz) 88 Figure S30. 1H NMR spectrum of 6c (CDCl3, 400 MHz) 89 Figure S31. 1H NMR spectrum of 6c (CD3OD, 400 MHz) 90 Figure S32. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 6c (CDCl3, 100 MHz) 91 Figure S33. 1H NMR spectrum of 6d (CDCl3, 400 MHz) 92 Figure S34. 1H NMR spectrum of 6d (CD3OD, 400 MHz) 93 Figure S35. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 6d (CDCl3, 50 MHz) 94 Figure S36. 1H NMR spectrum of 6e (CDCl3, 400 MHz) 95 Figure S37. 1H NMR spectrum of 6e (CD3OD, 400 MHz) 96 Figure S38. Supporting 1H NMR spectrum of 6e (CD3OD, 400 MHz) 97 Figure S39. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 6e (CDCl3, 50 MHz) 98 Figure S40. 1H NMR spectrum of 7 (CDCl3, 400 MHz) 99 Figure S41. 1H NMR spectrum of 8 (CDCl3, 400 MHz) 100 Figure S42. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 8 (CDCl3, 50 MHz) 101 Figure S43. 1H NMR spectrum of 9 (CDCl3, 400 MHz) 102 Figure S44. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 9 (CDCl3, 50 MHz) 103 Figure S45. 1H NMR spectrum of 10 (CDCl3, 200 MHz) 104 Figure S46. 13C NMR spectrum (DEPT-90, top; DEPT-135, middle; BBD, bottom) of 10 (CDCl3, 50 MHz) 105 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 粒線體醛去氫?2活化劑 | zh_TW |
| dc.subject | 人體乙醇代謝 | zh_TW |
| dc.subject | 臺灣黃柏 | zh_TW |
| dc.subject | Alda-1類似物 | zh_TW |
| dc.subject | 粒線體醛去氫?2活化劑 | zh_TW |
| dc.subject | 粒線體醛去氫?2 | zh_TW |
| dc.subject | 人體乙醇代謝 | zh_TW |
| dc.subject | 臺灣黃柏 | zh_TW |
| dc.subject | Alda-1類似物 | zh_TW |
| dc.subject | 粒線體醛去氫?2 | zh_TW |
| dc.subject | metabolism of ethanol | en |
| dc.subject | ALDH2 | en |
| dc.subject | ALDH2 activator | en |
| dc.subject | Alda-1 analogs | en |
| dc.subject | Phellodendron amurense var. wilsonii | en |
| dc.subject | metabolism of ethanol | en |
| dc.subject | ALDH2 | en |
| dc.subject | ALDH2 activator | en |
| dc.subject | Alda-1 analogs | en |
| dc.subject | Phellodendron amurense var. wilsonii | en |
| dc.title | Alda-1類似物之半合成、全合成及其對ALDH2之活性促進研究 | zh_TW |
| dc.title | Semi-synthesis, total synthesis and ALDH2 activating evaluations of Alda-1 analogs | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 李水盛;沈建昌 | zh_TW |
| dc.contributor.oralexamcommittee | Shoei-Sheng Lee;Chien-Chang Shen | en |
| dc.subject.keyword | 粒線體醛去氫?2,粒線體醛去氫?2活化劑,Alda-1類似物,臺灣黃柏,人體乙醇代謝, | zh_TW |
| dc.subject.keyword | ALDH2,ALDH2 activator,Alda-1 analogs,Phellodendron amurense var. wilsonii,metabolism of ethanol, | en |
| dc.relation.page | 105 | - |
| dc.identifier.doi | 10.6342/NTU201800590 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2018-02-14 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 藥學研究所 | - |
| 顯示於系所單位： | 藥學系 | |
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