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High-throughput Plasmodium falciparum growth assay for malaria drug discovery


, : High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Antimicrobial Agents and ChemoTherapy 51(2): 716-723

New therapeutic agents for the treatment of malaria, the world's most deadly parasitic disease, are urgently needed. Malaria afflicts 300 to 500 million people and results in I to 2 million deaths annually, and more than 85% of all malaria-related mortality involves young children and pregnant women in sub-Saharan Africa. The emergence of multidrug-resistant parasites, especially in Plasmodium falciparum, has eroded the efficacy of almost all currently available therapeutic agents. The discovery of new drugs, including drugs with novel cellular targets, could be accelerated with a whole-organism high-throughput screen (HTS) of structurally diverse small-molecule libraries. The standard whole-organism screen is based on incorporation of [H-3]hypoxanthine and has liabilities, such as limited throughput, high cost, multiple labor-intensive steps, and disposal of radioactive waste. Recently, screens have been reported that do not use radioactive incorporation, but their reporter signal is not robust enough for HTS. We report a P. falciparum growth assay that is technically simple, robust, and compatible with the automation necessary for HTS. The assay monitors DNA content by addition of the fluorescent dye 4',6-diamidino-2-phenylindole (DAPI) as a reporter of blood-stage parasite growth. This DA-PI P. falciparum growth assay was used to measure the 50% inhibitory concentrations (IC(50)s) of a diverse set of known antimalarials. The resultant IC(50)s compared favorably with those obtained in the [H-3] hypoxanthine incorporation assay. Over 79,000 small molecules have been tested for antiplasmodial activity using the DAPI P. falciparum growth assay, and 181 small molecules were identified as highly active against multidrug-resistant parasites.

US$19.90

PMID: 17116676

DOI: 10.1128/AAC.01144-06


Other references

Yoshikawa, G.Y.manaka, R., 1979: Adsorption of cation by humic v. Gakujutsu kenkyu hokoku = Research reports of the Kochi University Nogaku Kochi Daigaku8(28): 133-143

Khunkitti, W.; Avery, S.V.; Lloyd, D.; Furr, J.R.; Russell, A.D., 1997: Effects of biocides on Acanthamoeba castellanii as measured by flow cytometry and plaque assay. The lethal effects of various biocides, in particular two agents (chlorhexidine diacetate and polyhexamethylene biguanide) on cysts and trophozoites of Acanthamoeba castellanii have been measured by both plaque assay and flow cytometry (FCM). Mini...

Morgan, S.J.; Paolini, A.G., 2012: Behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach. Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural auditory prostheses, such as auditory brainstem implants and auditory midbrain implants. Whil...

Huppert, Oskar, 1928: Konstitution und Kon-figuration der Eiweissstoffe. The formation of proteins and carbohydrates, in nature, is brought about y a photochemical means from the system CO2 and NH8 in the presence of water. Carbamic acid (NH3COOH) is formed from the CO2 and NH3 which assumes the more reactive form imin...

Conte, K.P.; Odden, M.C.; Linton, N.M.; Harvey, S.Marie., 2016: Effectiveness of a Scaled-Up Arthritis Self-Management Program in Oregon: Walk With Ease. To evaluate the effectiveness of Walk With Ease (WWE), an evidence-based arthritis self-management program that was scaled up in Oregon in 2012 to 2014. Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework,...

Stein D.M.; Brinza S.R., 1989: The bulimia test factor structure in junior high school high school and college women. The present study examines the principal components structure of the Bulimia Test, developed originally with college women. In the present study, college women and junior high school and high school student samples from a rural catchment area were...

Esplugues, J.; Bedate, H.; Brugger, A., 1963: Mdi 193, A New Sulfonamide Diuretic. Medicina Clinica 41: 387-389

Alizadeh, A.; Hong, L.Z.; Kaelin, C.B.; Raudsepp, T.; Manuel, H.; Barsh, G.S., 2009: Genetics of Sex-linked yellow in the Syrian hamster. Alternating patches of black and yellow pigment are a ubiquitous feature of mammalian color variation that contributes to camouflage, species recognition, and morphologic diversity. X-linked determinants of this pattern--recognized by variegation...

Tsuji J.; Morifuku T.; Nakamura H.; Ito J.; Honjo I., 1990: Round window and promontory test for cochlear implant. Round window tests were clinically examined and compared with promontory tests in 6 cochlear implant candidates. The round window test results showed lower stimulating thresholds and wider dynamic ranges than the promontory tests. To test the prom...

Fischer, F.X., 1971: Problem of rational production and modern marketing of agricultural products. The main question discussed is whether the Swiss agricultural co-operative associations are fully in a position to support a modern orientation of production and marketing. The all Switzerland organizations founded to deal with special economic pr...