ArticleAntimicrobial agents and chemotherapy2015
Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
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- Indole-2-carboxamides Optimization for Antiplasmodial Activity.ACS bio & med chem Au · 2025Article
- Cell-Based Progression of Spiroindoline Phenotypic Hits Leads to the Identification of Compounds with Diverging Parasitological Profiles against the Human Malaria ParasiteJournal of medicinal chemistry · 2025Article
- Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola.Malaria journal · 2025Article
- Gossypol is a natural product with good antimalarial activity against Plasmodium falciparum clinical isolates.Scientific reports · 2025Article
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay.Antimicrobial agents and chemotherapy · 2024Article
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- Next Generation Chemiluminescent Probes for Antimalarial Drug Discovery.ACS infectious diseases · 2024Article
- Genetic complexity alters drug susceptibility of asexual and gametocyte stages ofAntimicrobial agents and chemotherapy · 2024Article
- IncompleteFrontiers in cellular and infection microbiology · 2024Article
- Fast-Killing Tyrosine Amide ((ACS infectious diseases · 2023Article
- Synthesis, Structure−Activity Relationships, and Parasitological Profiling of Brussonol Derivatives as New Plasmodium falciparum InhibitorsPharmaceuticals (Basel, Switzerland) · 2022Article
- Mechanistic basis for multidrug resistance and collateral drug sensitivity conferred to the malaria parasite by polymorphisms in PfMDR1 and PfCRT.PLoS biology · 2022Article
- PfMDR1 Transport Rates Assessed in Intact IsolatedPharmaceuticals (Basel, Switzerland) · 2022Article
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Assessing the Roles of Molecular Markers of Antimalarial Drug Resistance and the Host Pharmacogenetics in Drug-Resistant Malaria.Journal of tropical medicine · 2022Review
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs.
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