Pyrimethamine

Lumefantrine (AK Scientific, Union City, CA), chloroquine (Sigma-Aldrich, St. Louis, MO), pyrimethamine (AK Scientific), atovaquone (Sigma-Aldrich), and ferroquine (Medicines for Malaria Venture) were formulated in 1% methylcellulose (Acros Organics, Morris Plains, NJ) and 0.1% Tween 80 (Thermo Fisher Scientific, Fair Lawn, NJ) in double-distilled water. Piperaquine (AK Scientific) and artefenomel (Medicines for Malaria Venture) were formulated in 0.1% hydroxypropyl-methylcellulose (Sigma-Aldrich), 0.5% benzyl alcohol (Sigma-Aldrich), 0.4% Tween 80, 0.9% sodium chloride (Fisher Scientific, Loughborough, LE, UK) in double-distilled water. In some studies, Piperaquine was formulated in double-distilled water. Pyronaridine (Medicines for Malaria Venture) was formulated in 0.5% hydroxypropyl-methylcellulose and 0.1% Tween 80.
Before drug administration, each infected mouse was randomly assigned to its corresponding treatment. Drug treatment started when infected mice had ~1.4% patent parasitemia in peripheral blood (day 1 of study, designated P₀). The treatments were administered by oral gavage with 20-gauge straight reusable feeding needles (Fine Science Tools GmbH, Heidelberg, Germany). The volume of administration for the per os (p.o.) route was 10 mL/kg of body weight unless otherwise stated.

Twenty-eight compounds were tested for an herbicidal effect on A. thaliana. Eight commercially available herbicides were compared to twenty antimalarial compounds (Table 1). Amodiaquine, chloroquine, ciprofloxacin, glufosinate ammonium, glyphosate and oryzalin were obtained from Sigma-Aldrich. Artesunate was obtained from Pharbaco Central Pharmaceutical J.S.C., mefloquine from Roche, and asulam from Sapphire Bioscience. The rest (atovaquone, atrazine, azithromycin, clethodim, clindamycin, cycloguanil, dapsone, dicamba, dihydroartemisinin, doxycycline, halofantrine, lumefantrine, methacycline, piperaquine, primaquine, pyrimethamine, sulfadiazine, sulfadoxine, trifluralin) were sourced from AK Scientific. Stock solutions were prepared in DMSO, except chloroquine and glyphosate, which were prepared in water. Initial screening was at 20 μg/mL and the compounds that showed herbicidal activity were tested at a range of concentrations with DMSO as the negative control and four herbicides as positive controls.