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Antimicrob Agents Chemother. 1979 December; 16(6): 710-718
Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.
R E Desjardins,
C J Canfield,
J D Haynes and
J D Chulay
ABSTRACT
A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound tested. The applications and expectations of this new test system within a drug development program are discussed.
Antimicrob Agents Chemother. 1979 December; 16(6): 710-718
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Vial, H. J., Wein, S., Farenc, C., Kocken, C., Nicolas, O., Ancelin, M. L., Bressolle, F., Thomas, A., Calas, M.
(2004). Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl. Acad. Sci. USA
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Krief, S., Martin, M.-T., Grellier, P., Kasenene, J., Sevenet, T.
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48: 3196-3199
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Cameron, A., Read, J., Tranter, R., Winter, V. J., Sessions, R. B., Brady, R. L., Vivas, L., Easton, A., Kendrick, H., Croft, S. L., Barros, D., Lavandera, J. L., Martin, J. J., Risco, F., Garcia-Ochoa, S., Gamo, F. J., Sanz, L., Leon, L., Ruiz, J. R., Gabarro, R., Mallo, A., de las Heras, F. G.
(2004). Identification and Activity of a Series of Azole-based Compounds with Lactate Dehydrogenase-directed Anti-malarial Activity. J. Biol. Chem.
279: 31429-31439
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Rodrigues Goulart, H., Kimura, E. A., Peres, V. J., Couto, A. S., Aquino Duarte, F. A., Katzin, A. M.
(2004). Terpenes Arrest Parasite Development and Inhibit Biosynthesis of Isoprenoids in Plasmodium falciparum. Antimicrob. Agents Chemother.
48: 2502-2509
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Dow, G. S., Koenig, M. L., Wolf, L., Gerena, L., Lopez-Sanchez, M., Hudson, T. H., Bhattacharjee, A. K.
(2004). The Antimalarial Potential of 4-Quinolinecarbinolamines May Be Limited due to Neurotoxicity and Cross-Resistance in Mefloquine-Resistant Plasmodium falciparum Strains. Antimicrob. Agents Chemother.
48: 2624-2632
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Smilkstein, M., Sriwilaijaroen, N., Kelly, J. X., Wilairat, P., Riscoe, M.
(2004). Simple and Inexpensive Fluorescence-Based Technique for High-Throughput Antimalarial Drug Screening. Antimicrob. Agents Chemother.
48: 1803-1806
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BASCO, L. K.
(2004). MOLECULAR EPIDEMIOLOGY OF MALARIA IN CAMEROON. XX. EXPERIMENTAL STUDIES ON VARIOUS FACTORS OF IN VITRO DRUG SENSITIVITY ASSAYS USING FRESH ISOLATES OF PLASMODIUM FALCIPARUM. Am J Trop Med Hyg
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Teja-Isavadharm, P., Peggins, J. O., Brewer, T. G., White, N. J., Webster, H. K., Kyle, D. E.
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48: 954-960
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CORBETT, Y., HERRERA, L., GONZALEZ, J., CUBILLA, L., CAPSON, T. L., COLEY, P. D., KURSAR, T. A., ROMERO, L. I., ORTEGA-BARRIA, E.
(2004). A NOVEL DNA-BASED MICROFLUORIMETRIC METHOD TO EVALUATE ANTIMALARIAL DRUG ACTIVITY. Am J Trop Med Hyg
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Auparakkitanon, S., Noonpakdee, W., Ralph, R. K., Denny, W. A., Wilairat, P.
(2003). Antimalarial 9-Anilinoacridine Compounds Directed at Hematin. Antimicrob. Agents Chemother.
47: 3708-3712
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Locher, C. P., Ruben, P. C., Gut, J., Rosenthal, P. J.
(2003). 5HT1A Serotonin Receptor Agonists Inhibit Plasmodium falciparum by Blocking a Membrane Channel. Antimicrob. Agents Chemother.
47: 3806-3809
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Fleck, S. L., Birdsall, B., Babon, J., Dluzewski, A. R., Martin, S. R., Morgan, W. D., Angov, E., Kettleborough, C. A., Feeney, J., Blackman, M. J., Holder, A. A.
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Biagini, G. A., Richier, E., Bray, P. G., Calas, M., Vial, H., Ward, S. A.
(2003). Heme Binding Contributes to Antimalarial Activity of Bis-Quaternary Ammoniums. Antimicrob. Agents Chemother.
47: 2584-2589
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Ancelin, M. L., Calas, M., Vidal-Sailhan, V., Herbute, S., Ringwald, P., Vial, H. J.
(2003). Potent Inhibitors of Plasmodium Phospholipid Metabolism with a Broad Spectrum of In Vitro Antimalarial Activities. Antimicrob. Agents Chemother.
47: 2590-2597
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Mahmoudi, N., Ciceron, L., Franetich, J.-F., Farhati, K., Silvie, O., Eling, W., Sauerwein, R., Danis, M., Mazier, D., Derouin, F.
(2003). In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp.. Antimicrob. Agents Chemother.
47: 2636-2639
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Klenke, B., Barrett, M. P., Brun, R., Gilbert, I. H.
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(2003). In Vitro Activities of Piperaquine and Other 4-Aminoquinolines against Clinical Isolates of Plasmodium falciparum in Cameroon. Antimicrob. Agents Chemother.
47: 1391-1394
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NGO, T., DURAISINGH, M., REED, M., HIPGRAVE, D., BIGGS, B., COWMAN, A. F.
(2003). ANALYSIS OF PFCRT, PFMDR1, DHFR, AND DHPS MUTATIONS AND DRUG SENSITIVITIES IN PLASMODIUM FALCIPARUM ISOLATES FROM PATIENTS IN VIETNAM BEFORE AND AFTER TREATMENT WITH ARTEMISININ. Am J Trop Med Hyg
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NOEDL, H., FAIZ, M. A., YUNUS, E. B., RAHMAN, M. R., HOSSAIN, M. A., SAMAD, R., MILLER, R. S., PANG, L. W., WONGSRICHANALAI, C.
(2003). DRUG-RESISTANT MALARIA IN BANGLADESH: AN IN VITRO ASSESSMENT. Am J Trop Med Hyg
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ITTARAT, W., PICKARD, A. L., RATTANASINGANCHAN, P., WILAIRATANA, P., LOOAREESUWAN, S., EMERY, K., LOW, J., UDOMSANGPETCH, R., MESHNICK, S. R.
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Lim, P., Chy, S., Ariey, F., Incardona, S., Chim, P., Sem, R., Denis, M. B., Hewitt, S., Hoyer, S., Socheat, D., Merecreau-Puijalon, O., Fandeur, T.
(2003). pfcrt Polymorphism and Chloroquine Resistance in Plasmodium falciparum Strains Isolated in Cambodia. Antimicrob. Agents Chemother.
47: 87-94
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Waller, R. F., Ralph, S. A., Reed, M. B., Su, V., Douglas, J. D., Minnikin, D. E., Cowman, A. F., Besra, G. S., McFadden, G. I.
(2003). A Type II Pathway for Fatty Acid Biosynthesis Presents Drug Targets in Plasmodium falciparum. Antimicrob. Agents Chemother.
47: 297-301
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Ayi, K., Giribaldi, G., Skorokhod, A., Schwarzer, E., Prendergast, P. T., Arese, P.
(2002). 16{alpha}-Bromoepiandrosterone, an Antimalarial Analogue of the Hormone Dehydroepiandrosterone, Enhances Phagocytosis of Ring Stage Parasitized Erythrocytes: a Novel Mechanism for Antimalarial Activity. Antimicrob. Agents Chemother.
46: 3180-3184
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Wiesner, J., Henschker, D., Hutchinson, D. B., Beck, E., Jomaa, H.
(2002). In Vitro and In Vivo Synergy of Fosmidomycin, a Novel Antimalarial Drug, with Clindamycin. Antimicrob. Agents Chemother.
46: 2889-2894
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Ohrt, C., Willingmyre, G. D., Lee, P., Knirsch, C., Milhous, W.
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Riel, M. A., Kyle, D. E., Bhattacharjee, A. K., Milhous, W. K.
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Jones, K., Ward, S. A.
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46: 2700-2703
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Noedl, H., Wernsdorfer, W. H., Miller, R. S., Wongsrichanalai, C.
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Ziegler, H. L., Staerk, D., Christensen, J., Hviid, L., Hagerstrand, H., Jaroszewski, J. W.
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