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Background: possesses a cobalamin-dependent methionine synthase (MS). MS is putatively encoded by the PF3D7_1233700 gene, which is orthologous and syntenic in . However, its vulnerability as an antimalarial target has not been assessed.
Methods: We edited the PF3D7_1233700 and PF3D7_0417200 (dihydrofolate reductase-thymidylate synthase, DHFR-TS) genes and obtained transgenic parasites expressing epitope-tagged target proteins under the control of the ribozyme. Conditional loss-of-function mutants were obtained by treating transgenic parasites with glucosamine.
Results: DHFR-TS, but not MS mutants showed a significant proliferation defect over 96 h, suggesting that MS is not a vulnerable antimalarial target.
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http://dx.doi.org/10.7717/peerj.16595 | DOI Listing |
ACS Infect Dis
September 2025
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Malaria treatments are compromised by drug resistance, creating an urgent need to discover new drugs. We used a phenotypic high-throughput screening (HTS) platform to identify new antimalarials, uncovering three related pyrrole-, indole-, and indoline-based series with a shared α-azacyclic acetamide core. These compounds showed fast-killing activity on asexual blood-stage parasites, were not cytotoxic, and disrupted parasite intracellular pH and Na regulation similarly to cipargamin (KAE609), a clinically advanced inhibitor of the Na pump (ATP4).
View Article and Find Full Text PDFChem Biodivers
September 2025
Institute of Chemistry, Federal University of Catalão, Catalão, Brazil.
Strategies have been employed to address antimalarial drug resistance, including the exploration of new therapeutic targets. In this study, the stem bark of Dalbergia miscolobium was investigated using in vitro assays against Plasmodium falciparum and pyruvate kinase II (PyrKII), an essential enzyme for parasite development. Compounds were dereplicated from ethanolic extract (IC = 9 µg/mL) using LC-HRMS, revealing active constituents: procyanidin A1 (2), biochanin (5) and formononetin (7).
View Article and Find Full Text PDFMol Biochem Parasitol
September 2025
NyBerMan Bioinformatics Europe, Paddenstoelenlaan 8, Utrecht 3451 PZ, Netherlands.
The emergence of multidrug resistance in Plasmodium falciparum poses a serious threat to antimalarial treatment, particularly with growing resistance to artemisinin-based combination therapies (ACTs) and partner drugs like piperaquine. Mutations in key proteins, such as PfCRT (P. falciparum chloroquine resistance transporter) and PfDHFR (P.
View Article and Find Full Text PDFChem Biodivers
September 2025
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University Sub Campus, Dharashiv, India.
The present study aims to develop novel antimalarial and antimicrobial agents by synthesizing a series of 25 triazolyl quinoline carboxylate derivatives via azide-alkyne 1,3-dipolar cycloaddition, starting from isatin and p-fluoroacetophenone. Structural characterization was performed using IR, H NMR, C NMR, and mass spectrometry. The synthesized hybrids were evaluated for their in vitro antimalarial activity against the chloroquine-sensitive Plasmodium falciparum 3D7 strain.
View Article and Find Full Text PDFMini Rev Med Chem
August 2025
Department of Chemistry and Chemical Engineering, SBASSE, Lahore University of Management Sciences (LUMS), DHA, Lahore, 54792, Pakistan.
Quinoline is a biologically important bicyclic scaffold found in many natural products and medicinally relevant molecules. Quinoline-containing compounds continue to feature prominently in recent literature on hit identification and hit-to-lead campaigns targeting various biological pathways, underscoring the need for a review of the latest progress. This review presents recently reported quinoline-containing natural products, various synthetic methods for producing quinoline derivatives, and an overview of their diverse biological activities.
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