High-throughput Plasmodium falciparum growth assay for malaria drug discovery.

High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Research Abstract Details 

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High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Abstract Text:

Mary Lynn Baniecki,Dyann F Wirth,Jon Clardy,

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 1 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 [3H]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 DAPI P. falciparum growth assay was used to measure the 50% inhibitory concentrations (IC50s) of a diverse set of known antimalarials. The resultant IC50s compared favorably with those obtained in the [3H]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.

High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Publishing Authors By Initials

ML Baniecki,DF Wirth,J Clardy,

For similar reproductive and urinary physiology: reproduction: pregnancy research abstracts see: reproductive and urinary physiology: reproduction: pregnancy research

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High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Antimicrobial agents and chemotherapy

VOLUME: 51

Page Numbers: 716-23

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 0066-4804

DAY: 20

MONTH: 11

YEAR: 2006

High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 315061

High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Keywords Mesh Terms:

KEYWORDS: Pregnancy

MESH TERMS: growth & development

Chemical & Substance for Abstract: High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Information

Substance Name: DAPI

Registry Number: 47165-04-8

Grant and Affiliation Information for High-throughput Plasmodium falciparum growth assay for malaria drug discovery.

AFFILIATION: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, C-643, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R21NS053660

ACRONYM: NS

MEDLINETA: Antimicrob Agents Chemother

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