生物分子、硫醇和抗瘧藥物對於β-血紅素的生物礦化動力學之影響

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蔡旻翰(Ming-Han Tsai) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

生物分子、硫醇和抗瘧藥物對於β-血紅素的生物礦化動力學之影響
(The Effects of Biogenic Molecules, Thiol and Antimalarial Drugs on Biocrystallization Kinetics of β-Hematin Formation)

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摘要(中)

大約有40%的世界人口正處於可能遭受瘧疾感染的威脅。根據最新的統計，每年約有百餘萬的臨床病例並造成約80萬的死亡人數。瘧疾是由瘧原蟲所引起的，其中惡性瘧原蟲是造成死亡人數最多的一種瘧原蟲。雖然目前抗瘧疾藥物的治療效果良好，但是人與瘧疾的戰爭尚未結束，因為這些藥物廣泛的使用，造成了瘧疾對這些藥物逐漸產生抗藥性，所以有必要篩選及發展新的抗瘧疾藥物。目前有五種治療瘧疾的目標類型，我們著重於干擾其中hemozoin（β-hematin，其組成為ferriprotoporphyrin IX（Fe(III)PPIX））的生物結晶過程。在此論文中，我們不僅修飾了抗瘧疾藥物的篩選方法和成功的發現一種疑似可行的新藥物組合，並整合了hemozoin的生物結晶反應機制，也發現由不具催化效益的脂質（palmitic acid）和具有催化效益的脂質（1,2-dioleoyl-sn-gylcero-3-phosphocholine）混合後的脂質性質的重要性。

摘要(英)

About 40% of the world’s population lives in a threat from malaria infection. According to the current statistics, there were more than hundred millions of clinical cases and 800,000 deaths each year. Malaria was caused by Plasmodium parasites, which Plasmodium falciparum was one of the Plasmodium parasites that caused the most death in the world. Although the present antimalarial drugs worked well in treatments, the war against malaria was not over yet. Drug resistance began to develop due to the widely used of antimalarial drugs. Therefore, it is necessary to screen and develop new antimalarial drugs. There were five types of drug targets in malaria treatment, and we focused on interfering the biocrystallization process of hemozoin, also called β-hematin, formation (consists of ferriprotoporphyrin, Fe(III)PPIX). In this work, we not only modified the drug screening method for antimalarials and successfully developed a plausible drug combination to fight against malaria, but also mapped out the reaction mechanism for biocrystallization of hemozoin and discovered the importance of the lipid blends upon an active promoter (1,2-dioleoyl-sn-gylcero-3-phosphocholine) and an inactive promoter (palmitic acid).

關鍵字(中)

★ 結晶
★ 瘧疾
★ 硫醇
★ 抗瘧藥物
★ 血紅素
★ 生物礦化
★ 動力學
★ 生物分子

關鍵字(英)

★ biocrystallization
★ hematin
★ antimalarial drugs
★ thiol drugs
★ biogenic molecules
★ kinetics
★ malaria
★ crystal

論文目次

摘要 i
Abstract ii
Acknowledgement iii
Table of Contents iv
List of Tables viii
List of Figures ix
Chapter 1 Executive Summary 1
1.1 Introduction 1
1.2 History of Malaria 1
1.3 Life Cycle of Plasmodium falciparum 3
1.4 Currently Used Antimalarials 4
1.5 Conceptual Framework 7
1.6 References 9
Chapter 2 The Crystallization Mechanism and the Relationship between Hemozoin and β-Hematin 12
2.1 Introduction 12
2.2 The Characterizations of in vitro vs. in vivo 17
2.3 The Mechanisms of Hemozoin and β-Hematin Formation 21
2.3.1 Hemozoin Formation 21
2.3.2 β-Hematin Formation 23
2.4 The Recent Drug Screening Methods (in vitro) 26
2.5 The Instrumentation Methods for the Kinetic Studies on β-Hematin Formation (in vitro) 30
2.5.1 The FT-IR Method 30
2.5.2 The UV/vis Solid Method 31
2.5.3 The UV/vis Solution Method 32
2.6 Conclusions 33
2.7 References 34
Chapter 3 The Fundamental Properties of Hematin and β-Hematin 48
3.1 Introduction 48
3.2 Materials 49
3.3 Solvents 51
3.4 Experimental Procedures for Solubility Determination 54
3.5 Experimental Procedures for Solvent Screening of β-Hematin Formation 55
3.6 The Solubility of Hematin and Synthesized β-Hematin 56
3.7 Results and Discussion of Modified Solvent Screening Method 57
3.8 Conclusions 64
3.9 References 65
Chapter 4 The Effect of Biogenic Molecules, Thiol and Antimalarial Drugs on Biocrystallization Kinetics of β-Hematin Formation 67
4.1 Modified Rapid Screening (High-Throughput Screening) 67
4.2.1 Materials, Solvents, Solutions and Experimental Methods 70
4.2.2 Analytical Measurements 75
4.2.3 Results and Discussion 76
4.2.4 Conclusion 85
4.3 Kinetic Studies on β-Hematin Formation 87
4.3.1 Materials and Experimental Methods 88
4.3.2 Analytical Measurements 94
4.3.3 Results and Discussion 95
4.3.4 Conclusions 105
References 107
Chapter 5 Conclusions and Future Works 114
5.1 Newly Modified Rapid Screening Technique 114
5.2 Kinetic Studies of β-Hematin Formation 114
A.1 Introduction 116
A.2 Solution Phase 119
A.2.1 Ultraviolet-Visible Molecular Absorption Spectrometer (UV/vis) 119
A.3 Solid Phase 123
A.3.1 Powder X-ray Diffraction (PXRD) 123
A.3.2 Fourier Transform Infrared (FT-IR) Spectroscopy 126
A.3.3 Low Vacuum Scanning Electron Microscopy (LV-SEM) 129
A.4 Lipid Characterization 133
A.4.1 Low Temperature Differential Scanning Calorimetry (LT-DSC) 133
A.5 Conclusions 136
A.6 References 137
Appendix B List of Chemical Structures 142
Appendix C Supporting Information 144

參考文獻

Egan, T. J. Recent Advances in Understanding the Mechanism of Hemozoin (Malaria Pigment) Formation. J. Inorg. Biochem. 2008, 102 (5-6), 1288-1299.
Lancisi, G. M. De Noxiis Paludum Effluvius Eorumque Remediis; J. M. Salvioni: Rome, 1717.
Ross, R. On some Peculiar Pigmented Cells Found in Two Mosquitos Fed on Malarial Blood. Br. Med. J. 1897, 2 (1929), 1786-1788.
Brown, W. H. Malarial Pigment (so-called Melanin): Its Nature and Mode of Production. J. Exp. Med. 1911, 13 (2), 290-299.
Fitch, C. D.; Kanjananggulpan, P. The State of Ferriprotoporphyrin IX in Malaria Pigment. J. Biol. Chem. 1987, 262 (32), 15552-15555.
Hamsik, A. Preparation of Some Blood Pigment Derivatives. Z. Physiol. Chem. 1936, 190, 199-215.
Weissbuch, I.; Leiserowitz L. Interplay Between Malaria, Crystalline Hemozoin Formation, and Antimalarial Drug Action and Design. Chem. Rev. 2008, 108 (11), 4899-4914.
Hoang, A. N.; Sandlin, R. D.; Omar, A.; Egan, T. J.; Wright, D. W. The Neutral Lipid Composition Present in the Digestive Vacuole of Plasmodium falciparum Concentrates Heme and Mediates β-Hematin Formation with an Unusually Low Activation Energy. Biochemistry, 2010, 49 (47), 10107-10116.
Zhang, F.; Krugliak, M.; Ginsburg, H. The Fate of Ferriprotoporphyrin IX in Malaria Infected Erythrocytes in Conjunction with the Mode of Action of Antimalairal Drugs. Mol. Biochem. Parasitol. 1999, 99 (1), 129-141.
Loria, P.; Miller, S.; Tilley, L. Inhibition of the peroxidative degradation of Haem as the Basis of Action of Chloroquine and other Quinoline Antimalarials. Biochem. J. 1999, 339 (2), 363-370.
Egan, T. J.; Combrinck, J. M.; Egan, J.; Hearne, G. R.; Marques, H. M.; Ntenteni, S.; Sewell, B. T.; Smith, P. J.; Taylor, D.; van Schalkwyk, D. A.; Walden, J. C. Fate of Haem Iron in the Malaria Parasite Plasmodium falciparum. Biochem. J. 2002, 365 (2), 343-347.
Gligorijevic, B.; McAllister R.; Urbach, J. S.; Roepe, P. D. Spinning Disk Confocal Microscopy of Live, Intraerythrocytic Malarial Parasites. 1. Quantification of Hemozoin Development for Drug Sensitive versus Resistance Malaria. Biochemistry 2006, 45 (41), 12400-12410.
Slater, A. F. G.; Swiggard, W. J.; Orton, B. R.; Flitter, W. D.; Goldberg, D. E.; Cerami, A.; Handerson, G. B. An Iron-carboxylate Bond Links the Heme Units of Malaria Pigment. Proc. Natl. Acad. Sci. U. S. A., 1991, 88 (2), 325-329.
Bohle, D. S.; Dinnebier, R. E.; Madsen, S. K.; Stephens, P. W. Characterization of the Products of the Heme Detoxification Pathway in Malarial Late Trophozoites by X-ray Diffraction. J. Biol. Chem. 1997, 272 (2), 713-716.
Pagola, S.; Stephens, P. W.; Bohle, D. S.; Kosar, A. D.; Madsen, S. K. The Structure of Malaria Pigment β-Hematin. Nature 2000, 404 (6775), 307-310.
Klonis, N.; Dilanian, R.; Hanssen, E.; Darmanin, C.; Streltsov, V.; Deed, S.; Quiney, H.; Tilley, L. Hematin-Hematin Self-Association States Involved in the Formation and Reactivity of the Malaria Parasite Pigment, Hemozoin. Biochemistry, 2010, 49 (31), 6804-6811.
Noland, G. S.; Briones, N.; Sullivan Jr., D. J. The Shape and Size of Hemozoin Crystals Distinguishes Diverse Plasmodium Species. Mol. Biochem. Parasitol. 2003, 130 (2), 91-99.
Oliveira, M. F.; Kycia, S. W.; Gomez, A.; Kosar, A. J.; Bohle, D. S.; Hempelmann, E.; Menezes, D.; Vannier-Santos, M. A.; Oliveira, P. L.; Ferreira, S. T. Structural and Morphological Characterization of Hemozoin Produced by Schistosoma mansoni and Rhodnius prolixus. FEBS Lett. 2005, 579 (27), 6010-6016.
Bellemare, M.-J.; Bohle, D. S.; Brosseau, C.-N.; Georges, E.; Godbout, M.; Kelly, J.; Leimanis, M. L.; Leonelli, R.; Olivier, M.; Smilksterin, M. Autofluorescence of Condensed Heme Aggregates in Malaria Pigment and Its Synthetic Equivalent Hematin Anhydride (β-Hematin). J. Phys. Chem. B, 2009, 113 (24), 8391-8401.
Jaramillo, M.; Bellemare, M.-J.; Martel, C.; Shio, M. T.; Contreras, A. P.; Godbout, M.; Roger, M.; Gaudreault, E.; Gosselin, J.; Bohle, D. S.; Olivier, M. Synthethic Plasmodium-Like Hemozoin Activates the Immune Response: A Morphology – Function Study. PLoS One, 2009, 4 (9), e6957.
Slater, A. F. G.; Cerami, A. Inhibition by Chloroquine of a Novel Haem Polymerase Enzyme Activity in Malaria Trophozoites. Nature, 1992, 355 (6356), 167-169.
Egan, T. J.; Ross, D. C.; Adams, P. A. Quinoline Anti-malarial Drugs Inhibit Spontaneous Formation of β-Hematin (Malaria Pigment). FEBS Lett., 1994, 352 (1), 54-57.
Pandey, A. V.; Tekwani, B. L. Formation of Haemozoin/β-haematin Under Physiological Conditions is Not Spontaneous. FEBS Lett., 1996, 393 (2-3), 189-192.
Basilico, N.; Pagani, E.; Monti, D.; Olliaro, P.; Taramelli, D. A Microtitre-based Method for Measuring the Haem Polymerization Inhibitory Activity (HPIA) of Antimalarial Drugs. J. Antimicrob. Chemother. 1998, 42 (1), 55-60.
Tripathi, A. K.; Khan, S. I.; Walker, L. A.; Tekwani, B. L. Spectrophotometric Determination of de novo Hemozoin/β-Hematin Formation in an in vitro Assay. Anal. Biochem. 2004, 325 (1), 85-91.
Bohle, D. S.; Kosar, A. D.; Madsen, S. K. Propionic Acid Side Chain Hydrogen Bonding in the Malaria Pigment β-Hematin. Biochem. Biophys. Res. Commun., 2002, 294 (1), 132-135.
Frosch, T.; Koncarevic, S.; Becker, K.; Popp, J. Morphology-sensitive Raman Modes of the Malaria Pigment Hemozoin. Analyst, 2009, 134 (6), 1126-1132.
Stiebler, R.; Timm, B. L.; Oliveira, P. L.; Hearne, G. R.; Egan, T. J.; Oliveira, M. F. On the Physico-Chemical and Physiological requirements of Hemozoin formation Promoted by Perimicrovillar Membranes in Rhodnius prolixus Midgut. Insect Biochem. Mol. Biol. 2010, 40 (3), 284-292.
Parapini, S.; Basilico, N.; Mondani, M.; Olliaro, P.; Taramelli, D.; Monti, D. Evidence that Haem Iron in the Malaria Parasite is not Needed for the Antimalarial Effects of Artemisinin. FEBS Lett., 2004, 575 (1-3), 91-94.
Banerjee, R.; Liu, J.; Beatty, W.; Pelosof, L.; Klemba, M.; Goldberg, D. E. Four Plasmepsins are Active in the Plasmodium falciparum Food Vacuole, Including a Protease with an Active-site Histidine. Proc. Natl. Acad. Sci. U. S. A., 2002, 99 (2), 990-995.
Klemba, M.; Beatty, W.; Gluzman, I.; Goldberg, D. E. Trafficking of Plasmepsin II to the Food Vacuole of the Malaria Parasite Plasmodium falciparum. J. Cell. Biol., 2004, 164 (1), 47-56.
Sullivan Jr., D. J.; Gluzman, I. Y.; Russell, D. G.; Goldberg, D. E. On the Molecular Mechanism of Chloroquine’s Antimalarial Action. Proc. Natl. Acad. Sci. U. S. A., 1996, 93 (21), 11865-11870.
Saliba, K. J.; Folb, P. I.; Smith, P. J. Role for the Plasmodium falciparum Digestive Vacuole in Chloroquine Resistance. Biochem. Pharmacol. 1998, 56 (3), 313-320.
Oliveira, M. F.; Timm, B. L.; Machado, E. A.; Miranda, K.; Attias, M.; Silva, J. R.; Dansa-Petretski, M.; de Oliveira, M. A.; de Souza, W.; Pinhal, N. M.; Sousa, J. J. F.; Vugman, N. V.; Oliveira, P. L. On the Pro-oxidant Effects of Haemozoin. FEBS Lett., 2002, 512 (1-3), 139-144.
Sienkiewicz, A.; Krzystek, J.; Vileno, B.; Chatain, G.; Kosar, A. J. Multi-Frequency High-Field EPR Study of Iron Centers in Malarail Pigment. J. Am. Chem. Soc., 2006, 128 (14), 4534-4535.
Bohle, D. S.; Kosar, A. D.; Stephens, P. W. The Reversible Hydration of the Malaria Pigment β-Hematin. Can. J. Chem., 2003, 81 (11), 1285-1291.
Egan, T. J.; Mavuso, W. W.; Ncokazi, K. K. The Mechanism of β-Hematin Formation in Acetate Solution. Parallels Between Hemozoin formation and Biomineralization Processes. Biochemistry, 2001, 40 (1), 204-213.
Blauer, G.; Akkawi, M. Alcohol-Water as a Novel Medium for β-Hematin Preparation. Arch. Biochem. Biophys. 2002, 398 (1), 7-11.
Ncokazi, K. K.; Egan, T. J. A Colorimetric High-throughput β-Hematin Inhibition Screening Assay for Use in the Search for Antimalarial Compounds. Anal. Biochem., 2005, 338 (2), 306-319.
Egan, T. J.; Tshivhase, M. G. Kinetics of β-Hematin Formation from Suspensions of Haematin in Aqueous Benzoic Acid. Dalton Trans. 2006, 2006 (42), 5024-5032.
Egan, T. J.; Chen, J. Y-J.; de Villiers, K. A.; Mabotha, T. E.; Naidoo, K. J.; Ncokazi, K. K.; Langford, S. J.; McNaughton, D.; Pandiancherri, S.; Wood, B. R. Haemozoin (β-Haematin) Biomineralization Occurs by Self-Assembly Near the Lipid/Water Interface. FEBS Lett. 2006, 580 (21), 5105-5110.
Solomonv, I.; Osipova, M.; Feldman, Y.; Baehtz, C.; Kjaer, K.; Robinson, I. K.; Webster, G. T.; McNaughton, D.; Wood, B. R.; Weissbuch, I.; Leiserowitz, L. Crystal Nucleation, Growth, and Morphology of the Synthetic Malaria Pigment β-Hematin and the Effect Thereon by Quinoline Additives: The Malaria Pigment as a Target of Various Antimalarial Drugs. J. Am. Chem. Soc. 2007, 129 (9), 2615-2627.
Wang, X.; Ingall, E.; Lai, B.; Stack, A. G. Self-Assembled Monolayers as Templates for Heme Crystallization. Cryst. Growth Des., 2010, 10 (2), 798-805.
Hoang, A. N.; Ncokazi, K. K.; de Villiers, K. A.; Wright, D. W.; Egan, T. J. Crystallization of Synthetic Haemozoin (β-Haematin) Nucleated at the Surface of Lipid Particles. Dalton Trans., 2010, 39 (5), 1235-1244.
de Villers, K. A.; Osipova, M.; Mabotha, T. E.; Solomonov, I.; Feldman, Y.; Kjaer, K.; Weissbuch, I.; Egan, T. J.; Leiserowitz, L. Oriented Nucleation of β-Hematin Crystals Induced at Various Interfaces: Relevance to Hemozoin formation. Cryst. Growth Des. 2009, 9 (1), 626-632.
Blauer, G.; Akkawi, M. Investigations of B- and β-Hematin. J. Inorg. Biochem. 1997, 66 (2), 145-152.
Fitch, C. D.; Cai, G.-Z.; Chen, Y.-F.; Shoemaker, J. D. Involvement of Lipids in Ferriprotoporphyrin IX Polymerization in Malaria. Biochim. Biophys. Acta, 1999, 1454 (1), 31-37.
Goldberg, D. E.; Slater, A. F. G.; Cerami, A.; Henderson, G. B. Hemoglobin Degradation in the Malaria Parasite Plasmodium falciparum: An Ordered Process in a Unique Organelle. Proc. Natl. Acad. Sci. U. S. A. 1990, 87 (8), 2931-2935.
Chong, C. R.; Sullivan Jr., D. J. Inhibition of Heme Crystal Growth by Antimalarials and Other Compounds: Implications for Drug Discovery. Biochem. Pharmacol., 2003, 66 (11), 2201-2212 (2003).
Huy, N. T.; Maeda, A.; Uyen, D. T.; Trang, D. T. X.; Sasai, M.; Shiono, T.; Oida, T.; Harada, S.; Kamei, K. Alcohols Induced Beta-Hematin Formation via the Dissociation of Aggregated Heme and Reduction in Interfacial Tension of the Solution. Acta Trop. 2007, 101 (2), 130-138.
Walczak, M. S.; Lawniczk-Jablonska, K.; Wolska, A.; Sienkiewicz, A.; Suárez, L.; Kosar, A. J.; Bohle, D. S. Understanding Chloroquine Action at the Molecular Level in Antimalarial Therapy: X-ray Absorption Studies in Dimethyl Sulfoxide Solution. J. Phys. Chem. B, 2010, 115 (5), 1145-1150.
Adams, P. A.; Egan, T. J.; Ross, D. C.; Silver, J.; Marsh, P. J. The Chemical Mechanism of β-Haematin Formation Studied by Mӧssbauer Spectroscopy. Biochem. J. 1996, 318 (1), 25-27.
Puntharod, R.; Haller, K. J.; Wood, B. R. Investigation of Hematin in 0.1 M NaOH by Microscopy and Spectroscopy. Journal of the Microscopy Society of Thailand, 2010, 24 (2), 69-72.
Choi, C. Y. H.; Cerda, J. F.; Chu, H.-A.; Babcock, G. T.; Marletta, M. A. Spectroscopic Characterization of the Heme-Binding Sites in Plasmodium falciparum Histidine-Rich Protein 2. Biochemistry, 1999, 38 (51), 16916-16924.
Brown, S. B.; Dean, T. C.; Jones, P. Dimerization and Protolytic Equilibria of Protoferrihaem and Deuteroferrihaem in Aqueous Solution. Biochem. J. 1970, 117 (4), 733-739.
Collier, G. S.; Pratt, J. M.; de Wet, C. R.; Tshabalala, C. F. Studies on Haemin in Dimethyl Sulphoxide/water Mixtures. Biochem. J. 1979, 179 (2), 281-289.
Yayon, A.; Cabantchik, Z. I.; Ginsburg, H. Susceptibility of Human Malaria Parasites to Chloroquine is pH Dependent. Proc. Natl. Acad. Sci. U. S. A. 1985, 82 (9), 2784-2788.
Huy, N. T., Uyen, D. T., Sasai, M.; Trang, D. T. X.; Shiono, T.; Harada, S.; Kamei, K. A Simple and Rapid Colorimetric Method to Measure Hemozoin Crystal Growth in vitro. Anal. Biochem. 2006, 354 (2), 305-307.
Egan, T. J. Interactions of Quinoline Antimalarials with Hematin in Solution. J. Inorg. Biochem. 2006, 100 (5-6), 916-926.
de Villiers, K. A.; Kaschula, C. H.; Egan, T. J.; Marques, H. M. Speciation and Structure of Ferriprotoporphyrin IX in Aqueous Soltuion: Spectroscopic and Diffusion Measurements Demonstrate Dimerization, but not μ-oxo Dimer Formation. J. Biol. Inorg. Chem. 2007, 12 (1), 101-117.
Crespo, M.P.; Tilley, L.; Klonis, N. Solution Behavior of Hematin Under Acidic Conditions and Implications for Its Interactions with Chloroquine. J. Biol. Inorg. Chem. 2010, 15 (7), 1009-1022.
Casabianca, L. B.; An, D.; Natarajan, J. K.; Alumasa, J. N.; Roepe, P. D.; Wolf, C.; de Dios, A. C. Quinine and Chloroquine Differentially Pertub Heme Monomer-Dimer Equilibrium. Inorg. Chem. 2008, 47 (13), 6077-6081.
Jackson, K. E.; Klonis, N.; Ferguson, D. J. P.; Adisa, A.; Dogovski, C.; Tilley, L. Food Vacuole-associated Lipid Bodies and Heterogeneous Lipid Environments in the Malaria Parasite, Plasmodium falciparum. Mol. Microbiol. 2004, 54 (1), 109-122.
Pisciotta, J. M.; Coppens, I.; Tripathi, A. K.; Scholl, P. F.; Shuman, J.; Bajad, S.; Shulaev, V.; Sullivan Jr., D. J. The Role of Neutral Lipid Nanospheres in Plasmodium falciparum Haem Crystallization. Biochem. J. 2007, 402 (1), 197-204.
Klonis, N.; Tan, O.; Jackson, K.; Goldberg, D.; Klemba, M.; Tilley, L. Evaluation of pH During Cytostomal Endocytosis and Vacuolar Catabolism of Haemoglobin in Plasmodium falciparum. Biochem. J. 2007, 407 (3), 343-354.
Hayward, R.; Saliba, K. J.; Kirk, K. The pH of the Digestive Vacuole of Plasmodium falciparum is not Associated with Chloroquine Resistance. J. Cell Sci. 2006, 119 (6), 1016-1025.
Ziegler, J.; Linck, R.; Wright, D. W. Heme Aggregation Inhibitors: Antimalarial Drugs Targeting an Essential Biomineralization Process. Curr. Med. Chem. 2001, 8 (2), 171-189.
Hempelmann, E.; Egan, T. J. Pigment Biocrystallization in Plasmodium falciparum. Trends Parasitol. 2002, 18 (1), 11.
Egan, T. J. Haemozoin Formation. Mol. Biochem. Parasitol. 2008, 157 (2), 127-136.
Walczak, M. S.; Lawniczak-Jablonska, K.; Sienkiewicz, A.; Klepka, M. T.; Suarez, L.; Kosar, A. J.; Bellemare, M. J.; Bohle, D. S. XAFS Studies of the Synthetic Substitutes of Hemzoin. J. Non-Cryst. Solids 2010, 356 (37-40), 1908-1913.
Pasternack, R. F.; Munda, B.; Bickford, A.; Gibbs, E. J.; Scolaro, L. M. On the Kinetics of Formation of Hemozoin, the Malaria Pigment. J. Inorg. Biochem. 2010, 104 (10), 1119-1124.
Bohle, D. S.; Kosar, A. D.; Stephens, P. W. Phase Homogeneity and Crystal Morphology of the Malaria Pigment β-Hematin. Acta Crystallogr. Sect. D-Biol. Crystallogr. 2002, 58 (10-1), 1752-1756.
Asher, C.; de Villiers, K. A.; Egan, T. J. Speciation of Ferriprotoporphyrin IX in Aqueous and Mixed Aqueous Solution is Controlled by Solvent Identity, pH, and Salt Concentration. Inorg. Chem. 2009, 48 (16), 7994-8003.
Casagrande, M.; Basilico, N.; Rusconi, C.; Taramelli, D.; Sparatore, A.; Synthesis, Antimalarial Activity, and Cellular Toxicity of New Arylpyrrolylaminoquinolines. Bioorg. Med. Chem. 2010, 18 (18), 6625-6633.
Makler, M. T.; Ries, J. M; Williams, J. A.; Bancroft, J. E.; Piper, R. C.; Gibbins, B. L.; Hinrichs, D. J. Parasite Lactate Dehydrogenase as an Assay for Plasmodium falciparum Drug Sensitivity. Am. J. Trop. Med. Hyg. 1993, 48 (6), 739-741.
Monti, D.; Vodopivec, B.; Basilico, N.; Olliaro, P.; Taramelli, D. A Novel Endogenous Antimalarial: Fe(II)-Protoporphyrin IXα (Heme) Inhibits Hematin Polymerization to β-Hematin (Malaria Pigment) and Kills Malaria Parasites. Biochemistry 1999, 38 (28), 8858-8863.
Yayon, A.; Cabantchik, Z. I.; Ginsburg, H. Susceptibility of Human Malaria Parasites to Chloroquine is pH Dependent. Proc. Natl. Acad. Sci. U. S. A. 1985, 82 (9), 2784-2788.
Trang, D. T. X.; Huy, N. T.; Uyen, D. T.; Sasai, M.; Shiono, T.; Harada, S.; Kamei, K. Inhibition Assay of β-Hematin Formation Initiated by Lecithin for Screening New Antimalarial Drugs. Anal. Biochem. 2006, 349 (2), 292-296.
Ncokazi, K. K.; Egan, T. J. A Colorimetric High-throughput β-Hematin Inhibition Screening Assay for Use in the Search for Antimalarial Compounds. Anal. Biochem. 2005, 338 (2), 306-319.
Delarue-Cochin, S.; Paunescu, E.; Maes, L.; Mouray, E.; Sergheraert, C.; Grellier, P.; Melnyk, P. Synthesis and Antimalarial Activity of New Analogues of Amodiaquine. Eur. J. Med. Chem. 2008, 43 (2), 252-260.
Parapini, S.; Basilico, N.; Pasini, E.; Egan, T. J.; Olliaro, P.; Taramelli, D.; Monti, D. Standardization of the Physicochemical Parameters to Assess in Vitro the β-Hematin Inhibitory Activity of Antimalarial Drugs. Exp. Parasitol. 2000, 96 (4), 249-256.
Pasternack, R. F.; Munda, B.; Bickford, A.; Gibbs, E. J.; Scolaro, L. M. On the Kinetics of Formation of Hemozoin, the Malaria Pigment. J. Inorg. Biochem. 2010, 104 (10), 1119-1124.
Dorn, A.; Vippagunta, S. R.; Matile, H.; Jaquet, C.; Vennerstrom, J. L.; Ridley, R. G. An Assessment of Drug-Haematin Binding as a Mehcanism for Inhibition of Haematin Polymerisation by Quinoline Antimalarials. Biochem. Pharmacol. 1998, 55 (6), 727-736.
Vippagunta, S. R.; Dorn, A.; Matile, H.; Bhattacharjee, A. K.; Karle, J. M.; Ellis, W. Y.; Ridley, R. G.; Vennerstrom, J. L. Structural Specificity of Chloroquine-Hematin Binding Related to Inhibition of Hematin Polymerization and Parasite Growth. J. Med. Chem. 1999, 42 (22), 4630-4639.
Slater, A. F. G.; Swiggard, W. J.; Orton, B. R.; Flitter, W. D.; Goldberg, D. E.; Cerami, A.; Handerson, G. B. An Iron-carboxylate Bond Links the Heme Units of Malaria Pigment. Proc. Natl. Acad. Sci. U. S. A. 1991, 88 (2), 325-329.
Trang, D. T. X.; Huy, N. T.; Uyen, D. T.; Sasai, M.; Shiono, T.; Harada, S.; Kamei, K. Inhibition Assay of β-Hematin Formation Initiated by Lecithin for Screening New Antimalarial Drugs. Anal. Biochem. 2006, 349 (2), 292-296.

指導教授

李度(Tu Lee)

審核日期

2011-7-13

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