Microtubules as antiparasitic drug targets

Expert Opinion on Drug Discovery

Volumn 3, Issue 5, 2008, Pages 501-518

  Fennell, B J ^a,b   Naughton, J A ^a   Barlow, J ^c   Brennan, G ^d   Fairweather, I ^d   Hoey, E ^d   McFerran, N ^d   Trudgett, A ^d   Bell, A ^a  

^a School of Genetics and Microbiology   (Ireland)

^b UNIVERSITY COLLEGE DUBLIN   (Ireland)

^c ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

^d QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

Anthelmintic; Antiprotozoal drug; Drug design; Drug development; Microtubule; Parasite; Tubulin

Indexed keywords

ALBENDAZOLE; ALBENDAZOLE SULFOXIDE; ANTILEISHMANIAL AGENT; ANTIPARASITIC AGENT; BENZIMIDAZOLE DERIVATIVE; CHLORHEXIDINE; COLCHICINE; DIETHYLCARBAMAZINE; DOCETAXEL; DOLASTATIN; FEBANTEL; FENBENDAZOLE; HERBICIDE; IVERMECTIN; LEVAMISOLE; MEBENDAZOLE; METRONIDAZOLE; MICROTUBULE INHIBITOR; NETOBIMIN; OXFENDAZOLE; PACLITAXEL; PIPERAZINE DERIVATIVE; PRAZIQUANTEL; PYRANTEL; RHIZOXIN; TRICLABENDAZOLE; TUBULIN; UNINDEXED DRUG; VINBLASTINE; VINCA ALKALOID;

AMEBIASIS; ANTIMALARIAL ACTIVITY; ANTIPROTOZOAL ACTIVITY; BINDING SITE; CESTODIASIS; CYTOTOXICITY; DRUG ABSORPTION; DRUG BINDING; DRUG CHOICE; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG TARGETING; FASCIOLIASIS; FUNCTIONAL GENOMICS; GIARDIASIS; HELMINTHIASIS; HUMAN; IC 50; INFECTION CONTROL; MALARIA; MICROTUBULE; MULTIDRUG RESISTANCE; NEMATODIASIS; NONHUMAN; PARASITOSIS; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; TREMATODIASIS;

EID: 44649163877     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.5.501     Document Type: Review

References (138)

1. Cox FEG. Modern parasitology: a textbook of parasitology. 2nd edition. Oxford: Boston: Blackwell Science Publication; 1993
2. Khaw M, Panosian CB. Human antiprotozoal therapy: past, present, and Future. Clin Microbiol Rev 1995;8:427-39
3. Ouelette M, Ward S. Drug resistance in parasites. In: Marr JJ, Nilsen TW, Komuniecki RW, editors, Molecular medical parasitology. Academic Press: London; 2003. p. 397-432
4. Utzinger J, Keiser J. Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opin Pharmacother 2004;5:263-85
5. Wolstenholme AJ, Fairweather I, Prichard R, et al. Drug resistance in veterinary helminths. Trends Parasitol 2004;20:469-76
6. Albonico M, Engels D, Savioli L. Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control. Int J Parasitol 2004;34:1205-10
7. Jordan MA, Wilson L. Microtubules as a target far anticancer drugs. Nat Rev Cancer 2004;4:253-65
8. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Ann Rev Cell Dev Biol 1997;13:83-117
9. Morejohn LC, Fosket DE. The biochemistry of compounds with anti-microtubule activity in plant cells. Pharmacol Ther 1991;51:217-30
10. Gull K. The cytoskeleton of trypanosomatid parasites. Ann Rev Microbiol 1999;53:629-55
11. Morrissette NS, Sibley LD. Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev 2002;66:21-38; table of contents
12. Russell DG, Dubremetz JF. Microtubular cytoskeletons of parasitic protozoa. Parasitol Today 1986;2:177-9
13. Panda D, Miller HP, Banerjee A, et al. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci USA 1994;91:11358-62
14. Gigant B, Wang C, Ravelli RB, et al. Structural basis for the regulation of tubulin by vinblastine. Nature 2005;435:519-22
15. Nogales E. Structural insights into microtubule function. Ann Rev Biochem 2000;69:277-302
16. Nogales E, Wolf SG, Downing KH. Structure of the alpha beta tubulin dimer by electron crystallography. Nature 1998;391:199-203
17. Ravelli RB, Gigant B, Curmi PA, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004;428:198-202
18. Tuszynski JA, Carpenter EJ, Huzil JT, et al. The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos. Int J Dev Biol 2006;50:341-58
19. Hadfield JA, Ducki S, Hirst N, McGown AT. Tubulin and microtubules as targets for anticancer drugs. Prog Cell Cycle Res 2003;5:309-25
20. Werbovetz KA. Tubulin as an antiprotozoal drug target. Mini Rev Med Chem 2002;2:519-29
21. Banerjee M, Roy D, Bhattacharyya B, Basu G. Differential colchicine-binding across eukaryotic families: the role of highly conserved Pro268beta and Ala248beta residues in animal tubulin. FEBS Lett 2007;581:5019-23
22. Valdez J, Cedillo R, Hernandez-Campos A, et al. Synthesis and antiparasitic activity of 1H-benzimidazole derivatives. Bioorg Med Chem Lett 2002;12:2221-4
23. Kopanska K, Najda A, Zebrowska J, et al. Synthesis and activity of 1H-benzimidazole and 1H-benzotriazole derivatives as inhibitors of Acanthamoeba castellanii. Bioorg Med Chem 2004;12:2617-24
24. López-Vallejo F, Medina-Franco JL, Hernandez-Campos A, et al. Molecular modeling of some 1H-benzimidazole derivatives with biological activity against Entamoeba histolytica: a comparative molecular field analysis study. Bioorg Med Chem 2007;15:1117-26
25. Navarrete-Vazquez G, Cedillo R, Hernandez-Campos A, et al. Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives. Bioorg Med Chem Lett 2001;11:187-90
26. Navarrete-Vazquez G, Rojano-Vilchis Mde M, Yepez-Mulia L, et al. Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimidazole bioisosteres. Eur J Med Chem 2006;41:135-41
27. Navarrete-Vazquez G, Yepez L, Hernandez-Campos A, et al. Synthesis and antiparasitic activity of albendazole and mebendazole analogues. Bioorg Med Chem 2003;11:4615-22
28. Andrzejewska M, Yepez-Mulia L, Cedillo-Rivera R, et al. Synthesis, antiprotozoal and anticancer activity of substituted 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles. Eur J Med Chem 2002;37:973-8
29. Andrzejewska M, Yepez-Mulia L, Tapia A, et al. Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles. Eur J Pharm Sci 2004;21:323-9
30. Fairweather I. Triclabendazole: new skills to unravel an old(ish) enigma. J Helminthol 2005;79:227-34
31. Rivera N, Ibarra F, Zepeda A, et al. The effect of the 5-chloro-2-methylthio-6-(1-naphtyloxy)-1H-benzimidazole on the tegument of immature Fasciola hepatica in their natural host. Parasitol Res 2005;95:379-82
32. Hernández-Campos A, Ibarra-Velarde F, Vera-Montenegro Y, et al. Synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole. Chem Pharm Bull (Tokyo) 2002;50:649-52
33. Rivera N, Ibarra Velarde F, Olazaran JS. Efficacy of 5-chloro-2-methylthio-6-(1-naftiloxi)-1h-benzimidazole against different stages of Fasciola hepatica in Pelibuey sheep. Vet Mex 2002;33:55-61
34. Vera Montenegro Y, Ibarra Velarde F, Liebano Hernandez E., et al. Efficacy of an experimental fasciolicide against immature and mature Fasciola hepatica in artificially infected calves. Parasitol Res 2004;92:211-4
35. Vera Montenegro Y, Ibarra Velarde F, Quiroz Romero H, et al. Field trial on the efficacy of an experimental fasciolicide compared with some commercial compounds in naturally infected cattle. Parasitol Res 2003;91:1-4
36. McConville M, Brennan GP, McCoy M, et al. Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha. Parasitology 2006;133:195-208
37. McConville M, Brennan GP, McCoy M, et al. Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha. Parasitol Res 2007;100:365-77
38. McCoy M, McConville M, Brennan GP, et al. The efficacy of the experimental fasciolicide, compound alpha against triclabendazole-resistant Fasciola hepatica infections in sheep. Proceedings of the 11th International Congress of Parasitology (ICOPA XI); Glasgow, Scotland; 2006
39. Mavrova A, Anichina KK, Vuchev DI, et al. Synthesis and antitrichinellosis activity of some 2-substituted-[1,3]thiazolo[3,2-a] benzimidazol-3(2H)-ones. Bioorg Med Chem 2005;13:5550-9
40. Yépez-Mulia L, Morales-Hurtado R, Viveros-Guzman N, et al. Evaluation of albendazole prodrugs in experimental trichinellosis. Arch Med Res 1999;30:368-74
41. Dumonter C. Mechanisms of action and resistance to tubulin-binding agents. Expert Opin Investig Drugs 2000;9:779-88
42. Fennell BJ, Carolan S, Pettit GR, Bell A. Effects of the antimitotic natural product dolastatin 10, and related peptides, on the human malarial parasite Plasmodium falciparum. J Antimicrob Chemother 2003;51:833-41
43. Gull K, Birkett C, Gerke-Bonet R, et al. The cell cycle and cytoskeletal morphogenesis in Trypanosoma brucei. Biochem Soc Trans 1990;18:720-2
44. Ganesh T, Guza RC, Bane S, et al. The bioactive Taxol conformation on beta-tubulin: experimental evidence from highly active constrained analogs. Proc Natl Acad Sci USA 2004;101:10006-11
45. Kapoor P, Sachdeva M, Madhubala R. Effect of the microtubule stabilising agent taxol on leishmanial protozoan parasites in vitro. FEMS Microbiol Lett 1999;176:429-35
46. Chan MM, Fong D. Inhibition of leishmanias but not host macrophages by the antitubulin herbicide trifluralin. Science 1990;249:924-6
47. Fennel] BJ, Naughton JA, Dempsey E, Bell A. Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target. Mol Biochem Parasitol 2006;145:226-38
48. Stokkermans TJ, Schwartzman JD, Keenan K, et al. Inhibition of Toxoplasma gondii replication by dinitroaniline herbicides. Exp Parasitol 1996;84:355-70
49. Werbovetz KA, Sackett DL, Delfin D, et al. Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (GB-II-5) against kinetoplastid parasites. Mol Pharmacol 2003;64:1325-33
50. Morejohn LC, Bureau TE, Molè-Bajer J, et al. Oryzalin, a dinitroaniline herbicide, binds to plant tubulin and inhibits microtubule polymerization in vitro. Planta (Berl) 1987;172(2):252-64
51. Morejohn LC, Fosket DE. Inhibition of plant microtubule polymerisation in vitro by the phosphoric amide herbicide amiprophos-methyl. Science 1984;224:874-6
52. Hoffman JC, Vaughn KC. Mitotic disrupter herbicides act by a single mechanism but vary in efficacy. Protoplasma 1994;179:16-25
53. Traub-Cseko YM, Ramalho-Ortigao JM, Dantas AP, et al. Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma cruzi. Trends Parasitol 2001;17:136-41
54. Bhattacharya G, Herman J, Delfin D, et al. Synthesis and antitubulin activity of N1- and N4-substituted 3,5-dinitro sulfanilamides against African trypanosomes and Leishmania. J Med Chem 2004;47:1823-32
55. George TG, Johnsamuel J, Delfin DA, et al. Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides. Bioorg Med Chem 2006;14:5699-710
56. Anthony RG, Waldin TR, Ray JA, et al. Herbicide resistance caused by spontaneous mutation of the cytoskeletal protein tubulin. Nature 1998;393:260-3
57. Ma C, Li C, Ganesan L, et al. Mutations in {alpha}-tubulin confer dinitroaniline resistance at a cost to microtubule function. Mol Biol Cell 2007;18:4711-20
58. Morrissette NS, Mitra A, Sept D, Sibley LD. Dinitroanilines bind alpha-tubulin to disrupt microtubules. Mol Biol Cell 2004;15:1960-8
59. Blume YB, Nyporko AY, Yemets AI, Baird WV. Structural modeling of the interaction of plant alpha-tubulin with dinitroaniline and phosphoroamidate herbicides. Cell Biol Int 2003;27:171-4
60. Délye C, Menchari Y, Michel S, Darmency H. Molecular bases for sensitivity to tubulin-binding herbicides in green foxtail. Plant Physiol 2004;136:3920-32
61. Mitra A, Sept D. Binding and interaction of dinitroanilines with apicomplexan and kinetoplastid alpba-tubulin. J Med Chem 2006;49:5226-31
62. James SW, Lefebvre PA. Genetic interactions among Chlamydomonas reinhardtii mutations that confer resistance to anti-microtubule herbicides. Genetics 1992;130:305-14
63. Callahan H, Kelley C, Grogl M, Schuster BG. Compositions having anti-leishmanial activity. US6433023 (2002)
64. Best WM, Sims CG, Thompson RCA, et al. Antiparasitic compounds. WO/2006/ 108224 (2006)
65. George TG, Endeshaw MM, Morgan RE, et al. Synthesis, biological evaluation, and molecular modeling of 3,5-substituted-N1-phenyl-N4,N4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents. Bioorg Med Chem 2007;15:6071-9
66. Hiam A, Sebastien D, George B, et al. Microtubule target for new antileishmanial drugs based on ethyl 3-haloacetamidobenzoates. J Enzyme Inhib Med Chem 2006;21:305-12
67. Dieckmann-Schuppert A, Franklin RM. Compounds binding to cytoskeletal proteins are active against Plasmodium falciparum in vitro. Cell Biol Int Rep 1989;13:411-8
68. Bell A, Wernli B, Franklin RM. Effects of microtubule inhibitors on protein synthesis in Plasmodium falciparum. Parasitol Res 1993;79:146-52
69. Fong D. Effect of the anti-microtubule compound tubulozole on Leishmania protozoan parasites in vitro. FEMS Microbiol Lett 1993;107:95-9
70. Robinson MW, Trudgett A, Hoey EM, Fairweather I. The effect of the microtubule inhibitor tubulozole-C on the tegument of triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica. Parasitol Res 2003;91:117-29
71. Stitt AW, Fairweather I. Spermatogenesis in Fasciola hepatica: and ultrastructural comparison of the effects of the anthelmintic, triclabendazole ("Fasinex") and the microtubule inhibitor, tubulozole-C. Invertebr Reprod Dev 1992;22:139-50
72. Stitt AW, Fairweather I. Fasciola hepatica: the effect of the microtubule inhibitors colchicine and tubulozole-C on the ultrastructure of the adult fluke. Parasitology 1993;107:297-309
73. Billker O, Shaw MK, Jones IW, et al. Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei. J Eukaryot Microbiol 2002;49:489-97
74. Bhattacharya G, Salem MM, Werbovetz KA. Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin. Bioorg Med Chem Lett 2002;12:2395-8
75. Werbovetz KA, Brendle JJ, Sackett DL. Purification, characterization, and drug susceptibility of tubulin from Leishmania. Mol Biochem Parasitol 1999;98:53-65
76. MacDonald LM, Armson A, Thompson AR, Reynoldson JA. Characterisation of benzimidazole binding with recombinant tubulin from Giardia duodenalis, Encephalitozoon intestinalis, and Cryptosporidium parvum. Mol Biochem Parasitol 2004;138:89-96
77. Mayer TU, Kapoor TM, Haggarty SJ, et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999;286:971-4
78. Kim JY, Pannell LK, Sackett DL. Mass spectrometric measurement of differential reactivity of cysteine to localize protein-ligand binding sites. Application to tubulin-binding drugs. Anal Biochem 2004;332:376-83
79. Lowe J, Li H, Downing KH, Nogales E. Refined structure of alpha beta-tubulin at 3.5 A resolution. J Mol Biol 2001;313:1045-57
80. Kim YJ, Sackett DL, Schapira M, et al. Identification of 12Cysbeta on tubulin as the binding site of tubulyzine. Bioorg Med Chem 2006;14:1169-75
81. Nguyen TL, McGrath C, Hermone AR, et al. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J Med Chem 2005;48:6107-16
82. Carpenter EJ, Huzil JT, Luduena RF, Tuszynski JA. Homology modeling of tubulin: influence predictions for microtubule's biophysical properties. Eur Biophys J 2006;36:35-43
83. Robinson MW, McFerran N, Trudgett A, et al. A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement. J Mol Graph Model 2004;23:275-84
84. Warner SL, Gray PJ, Von Hoff DD. Tubulin-associated drug targets: Aurora kinases, Polo-like kinases, and others. Semin Oncol 2006;33:436-48
85. Duhl DM, Renhowe PA. Inhibitors of kinesin motor proteins - research and clinical progress. Curr Opin Drug Discov Devel 2005;8:431-6
86. Fowler RE, Smith AM, Whitehorn J, et al. Microtubule associated motor proteins of Plasmodium falciparum merozoites. Mol Biochem Parasitol 2001;117:187-200
87. Takagi H, Islam MZ, Itoh M, et al. Short report: production of recombinant kinesin-related protein of Leishmania donovani and its application in the serodiagnosis of visceral leishmaniasis. Am J Trop Med Hyg 2007;76:902-5
88. Cyrklaff M, Kudryashev M, Leis A, et al. Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites. J Exp Med 2007;204:1281-7
89. Lubega GW, Geary TG, Klein RD, Prichard RK. Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and mebendazole. Mol Biochem Parasitol 1993;62:281-92
90. Bell A. Microtubule inhibitors as potential antimalarial agents. Parasitol Today 1998;14:234-40
91. Kappes B, Rohrbach P. Microtubule inhibitors as a potential treatment for malaria. Future Microbiol 2007;2:409-23
92. Aguirre-Cruz L, Calderon M, Sotelo J. Colchicine decreases the infection by Toxoplasma gondii in cultured glial cells. J Parasitol 1996;82:325-7
93. Estes R, Vogel N, Mack D, McLeod R. Paclitaxel arrests growth of intracellular Toxoplasma gondii. Antimicrob Agents Chemother 1998;42:2036-40
94. Morrissette NS, Sibley LD. Disruption of microtubules uncouples budding and nuclear division in Toxoplasma gondii. J Cell Sci 2002;115:1017-25
95. Mead JR, Fauq AH, Khan MA, McNair N. Efficacy of glycoconjugated dinitroanilines against Cryptosporidium parvum. J Eukaryot Microbiol 2003;50(Supp 1):550-2
96. Wiest PM, Johnson JH, Flanigan TP. Microtubule inhibitors block Cryptosporidium parvum infection of a human enterocyte cell line. Infect Immun 1993;61:4888-90
97. Russell DG, Sinden RE. The role of the cytoskeleton in the motility of coccidian sporozoites. J Cell Sci 1981;50:345-59
98. Chan MM, Grogl M, Chen CC, et al. Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. Proc Natl Acad Sci USA 1993;90:5657-61
99. Kaminsky R, Zweygarth E. Feeder layer-free in vitro assay for screening antitrypanosomal compounds against Trypanosoma brucei brucei and T. b. evansi. Antimicrob Agents Chemother 1989;33:881-5
100. Lubega GW, Ochola DO, Prichard RK. Trypanosoma brucei: anti-tubulin antibodies specifically inhibit trypanosome growth in culture. Exp Parasitol 2002;102:134-42
101. Turrens JF, Watts BP Jr, Zhong L, Docampo R. Inhibition of Trypanosoma cruzi and T. brucei NADH fumarate reductase by benznidazole and anthelmintic imidazole derivatives. Mol Biochem Parasitol 1996;82:125-9
102. Baum SG, Wittner M, Nadler JP, et al. Taxol, a microtubule stabilizing agent, blocks the replication of Trypanosoma cruzi. Proc Natl Acad Sci USA 1981;78:4571-5
103. Bogitsh BJ, Middleton OL, Ribeiro-Rodrigues R. Effects of the antitubulin drug trifluralin on the proliferation and metacyclogenesis of Trypanosoma cruzi epimastigotes. Parasitol Res 1999;85:475-80
104. Filho SA, Pereira de Almeida ER, Gander ES. The influence of hydroxyurea and colchicine on growth and morphology of Trypanosoma cruzi. Acta Trop 1978;35:229-37
105. Grellier P, Sinou V, Schrevel J. Differential actions of antimicrotubular drugs on the development of Trypanosoma cruzi, the agent of Chagas' disease. Biol Cell 1995;84:92-1
106. Callahan HL, Kelley C, Pereira T, Grogl M. Microtubule inhibitors: structure-activity analyses suggest rational models to identify potentially active compounds. Antimicrob Agents Chemother 1996;40:947-52
107. Armson A, Kamau SW, Grimm F, et al. A comparison of the effects of a benzimidazole and the dinitroanilines against Leishmania infantum. Acta Trop 1999;73:303-11
108. Jayanarayan KG, Dey CS. Altered tubulin dynamics, localization and post-translational modifications in sodium arsenite resistant Leishmania donovani in response to paclitaxel, trifluralin and a combination of both and induction of apoptosis-like cell death. Parasitology 2005;131:215-30
109. Katiyar SK, Gordon VR, McLaughlin GL, Edlind TD. Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence. Antimicrob Agents Chemother 1994;38:2086-90
110. Dawson SC, Sagolla MS, Mancuso JJ, et al. Kinesin-13 regulates flagellar, interphase, and mitotic microtubule dynamics in Giardia intestinalis. Eukaryot Cell 2007
111. Menon KI. Assessment of the antiprotozoal activity of some tubulin inhibitors following cyclodextrin complexation: Murdoch University Australia; 2002
112. Morgan UM, Reynoldson JA, Thompson RC. Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro. Antimicrob Agents Chemother 1993;37:328-31
113. Juliano C, Martinotti MG, Cappuccinelli P. "In vitro" effect of microtubule inhibitors on Trichomonas vaginalis. Microbiologica 1985;8:31-42
114. Fritsch FM, Mehlhorn H, Schein E, Hauser M. The effects of drugs on the formation of Theileria annulata merozoites in vitro. Parasitol Res 1988;74:340-3
115. Dastidar PG, Majumder S, Lohia A. Eh Klp5 is a divergent member of the kinesin 5 family that regulates genome content and microtubular assembly in Entamoeba histolytica. Cell Microbiol 2007;9:316-28
116. Makioka A, Kumagai M, Kobayashi S, Takeuchi T. Inhibition of excystation and metacystic development of Entamoeba invadens by the dinitroaniline herbicide oryzalin. J Parasitol 2002;88:994-9
117. Makioka A, Kumagai M, Ohtomo H, et al. DNA polymerase activity in encysting Entamoeba invadens. Parasitol Res 1999;85:604-6
118. Katiyar SK, Edlund TD. In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives. Antimicrob Agents Chemother 1997;41:2729-32
119. Ridoux O, Drancourt M. In vitro susceptibilities of die microsporidia Encephalitozoon cuniculi, Encephalitozoan hellem, and Encephalitozoon intestinalis to albendazole and its sulfoxide and sulfone metabolites. Antimicrob Agents Chemother 1998;42:3301-3
120. Levy YY, Lai EY, Remillard SP, Fulton C. Centrin is synthesized and assembled into basal bodies during Naegleria differentiation. Cell Motil Cytoskeleton 1998;40:249-60
121. McBride J, Ingram PR, Henriquez FL, Roberts CW. Development of colorimetric microtiter plate assay for assessment of antimicrobials against Acanthamoeba. J Clin Microbiol 2005;43:629-34
122. Henriquez FL, Ingram PR, Muench SP, et al. Molecular basis for resistance of Acanthamoeba tubulins to all major classes of antitubulin compounds. Antimicrob Agents Chemother 2008;52:1133-5
123. Pouvelle B, Farley PJ, Long CA, Taraschi TF. Taxol arrests the development of blood-stage Plasmodium falciparum in vitro and Plasmodium chabaudi adami in malaria-infected mice. J Clin Invest 1994;94:413-7
124. Seitz HM, Gottwald F, Proft J, et al. Docetaxel (Taxotere): effectiveness against Plasmodium falciparum in vitro and Plasmodium yoelii nigeriensis in vivo. Tokai J Exp Clin Med 1998;23:427-30
125. Farthung MJ. Treatment options for the eradication of intestinal protozoa. Nat Clin Pract Gastroenterol Hepatol 2006;3:436-45
126. Fayer R, Fetterer R. Activity of benzimidazoles against cryptosporidiosis in neonatal BALB/c mice. J Parasitol 1995;81:794-5
127. Zaidenberg A, Luong T, Lirussi D, et al. Treatment of experimental chronic chagas disease with trifluralin. Basic Clin Pharmacol Toxicol 2006;98:351-6
128. Chan MM, Tzeng J, Emge TJ, et al. Structure-function analysis of antimicrotubule dinitroanilines against promastigotes of the parasitic protozoan Leishmania mexicana. Antimicrob Agents Chemother 1993;37:1909-13
129. Travi B, Osorio Y. Failure of albendazole as an alternative treatment of cutaneous leishmaniasis in the hamster model. Mem Inst Oswaldo Cruz 1998;93:515
130. Escobedo AA, Canete R, Gonzalez ME, et al. A randomized trial comparing mebendazole and secnidazole for the treatment of giardiasis. Ann Trop Med Parasitol 2003;97:499-504
131. Escobedo AA, Nunez FA, Moreira I, et al. Comparison of chloroquine, albendazole and tinidazole in the treatment of children with giardiasis. Ann Trop Med Parasitol 2003;97:367-71
132. Hall A, Nahar Q. Albendazole as a treatment for infections with Giardia duodenalis in children in Bangladesh. Trans R Soc Trop Med Hyg 1993;87:84-6
133. Karabay O, Tamer A, Gunduz H, et al. Albendazole versus metronidazole treatment of adult giardiasis: an open randomized clinical study. World J Gastroenterol 2004;10:1215-7
134. Pengsaa K, Sirivichayakul C, Pojjaroen-anant C, et al. Albendazole treatment for Giardia intestinalis infections in school children. Southeast Asian J Trop Med Public Health 1999;30:78-83
135. Yereli K, Balcioglu IC, Ertan P, et al. Albendazole as an alternative therapeutic agent for childhood giardiasis in Turkey. Clin Microbiol Infect 2004;10:527-9
136. Molina JM, Chastang C, Goguel J, et al. Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial. J Infect Dis 1998;177:1373-7
137. Dore GJ, Marriott DJ, Hing MC, et al. Disseminated microsporidiosis due to Septata intestinalis in nine patients infected with the human immunodeficiency virus: response to therapy with albendazole. Clin Infect Dis 1995;21:70-6
138. Gross U. Treatment of microsporidiosis including albendazole. Parasitol Res 2003;90(Supp 1):S14-8