Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.
TLDR
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, and results demonstrated that the method is sensitive and precise.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.read more
Citations
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Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept'.
TL;DR: This review provides a number of recommendations that will help to define a more sound 'proof-of-concept' for antibacterial, antifungal, antiviral and antiparasitic potential in natural products.
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Mutations in the P. falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance
David A. Fidock,Takashi Nomura,Angela K. Talley,Roland A. Cooper,Sergey M. Dzekunov,Michael T. Ferdig,Lyann M. B. Ursos,Amar Bir Singh Sidhu,Bronwen Naudé,Kirk W. Deitsch,Xin-zhuan Su,John C. Wootton,Paul D. Roepe,Thomas E. Wellems +13 more
TL;DR: The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7 that harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America.
Journal ArticleDOI
Simple and Inexpensive Fluorescence-Based Technique for High-Throughput Antimalarial Drug Screening
TL;DR: A side-by-side comparison of this new fluorescence assay and a standard radioisotopic method suggest that it may be an ideal method for high-throughput antimalarial drug screening.
Journal ArticleDOI
Thousands of chemical starting points for antimalarial lead identification
Francisco-Javier Gamo,Laura M. Sanz,J. Vidal,Cristina de Cozar,Emilio Alvarez,J.L. Lavandera,Dana E. Vanderwall,Darren V. S. Green,Vinod Kumar,Samiul Hasan,James R. Brown,Catherine E. Peishoff,Lon R. Cardon,Jose F. Garcia-Bustos +13 more
TL;DR: Chemical structures and associated data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host–pathogen interaction related targets.
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Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.
TL;DR: Direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine is provided, which has important implications for the development and efficacy of future antimalarial agents.
References
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