A genetically homogeneous population of Plasmodium falciparum prepared by a single erythrocyte micromanipulation technique was used to produce lines of P. falciparum resistant to mefloquine hydrochloride in vitro. Parasites were maintained in a culture medium containing gradually increased concentrations of mefloquine hydrochloride (CMP-mef) starting with 2 ng/ml. One of the mefloquine-resistant culture lines (W2-mef) was obtained after 96 weeks of continuous culture in CMP-mef, the last 4 weeks in medium containing 40 ng/ml of mefloquine hydrochloride. The W2-mef was four to six times more resistant to mefloquine than was the parent clone W2. Means of multiple determinations of 50% inhibitory concentrations (IC-50) of mefloquine hydrochloride against W2-mef and clone W2 were 20.39 +/- 5.08 ng/ml and 4.50 +/- 1.94 ng/ml, respectively.
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http://dx.doi.org/10.1016/0014-4894(88)90082-3 | DOI Listing |
Microorganisms
December 2024
Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France.
Currently, artemisinin-based combination therapy is recommended as first-line treatment of uncomplicated malaria. Arylamino alcohols (AAAs) such as mefloquine (MQ) are the preferred partner drugs due to their longer half-life, reliable absorption and strong antimalarial activity. However, the mode of action of MQ remains poorly understood and its neurotoxicity limits its use.
View Article and Find Full Text PDFPLoS One
December 2024
Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
Gap junction intercellular communication (GJIC) between two adjacent cells involves direct exchange of cytosolic ions and small molecules via connexin gap junction channels (GJCs). Connexin GJCs have emerged as drug targets, with small molecule connexin inhibitors considered a viable therapeutic strategy in several diseases. The molecular mechanisms of GJC inhibition by known small molecule connexin inhibitors remain unknown, preventing the development of more potent and connexin-specific therapeutics.
View Article and Find Full Text PDFCureus
November 2024
Department of Pediatrics, Teikyo University School of Medicine, Tokyo, JPN.
Background Alveolar echinococcosis (AE) is a fatal zoonotic disease distributed mainly in the Northern Hemisphere. At present, its curative treatment relies on surgery, and the development of effective drugs is needed. We previously demonstrated the anti-echinococcal effect of atovaquone (ATV) as a mitochondrial complex III inhibitor in both in vitro and in vivo experiments.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Praziquantel alone is insufficient for the control of schistosomiasis due to poor efficacy against juvenile worms and increasing concerns about the risk of drug resistance. We compared the efficacy and safety of praziquantel combined with four different artemisinin-based combinations to praziquantel alone in treating infection in Kenyan children. In this randomized, open-label, five-arm, head-to-head, non-inferiority trial, children (aged 9-15 years) with infection according to duplicate Kato Katz thick smears from a stool sample in the Mwea irrigation scheme of central Kenya, were enrolled.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
School of Public Health, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.
Antimicrobial resistance is among the greatest threats to public health globally, and drug repurposing strategies may be advantageous to addressing this problem. Mefloquine, a drug traditionally used to treat malaria, has emerged as a promising antibiotic adjuvant, due to its ability to enhance the effectiveness of conventional antibiotics against resistant bacterial strains. In this paper, we first outline the enhancement properties of mefloquine and its mechanisms of action as an adjuvant antibiotic against multidrug-resistant bacteria.
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