Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The sodium efflux pump ATP4 is a leading antimalarial target, but suffers from a lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design of next generation inhibitors. Here, we determine a 3.7Å cryoEM structure of ATP4 purified from CRISPR-engineered parasites, revealing a previously unknown, apicomplexan-specific binding partner, ABP, which forms a conserved, likely modulatory interaction with ATP4. The discovery of ABP presents a new avenue for designing novel ATP4 inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888398 | PMC |
| http://dx.doi.org/10.1101/2025.02.25.640208 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of α-Azacyclic Acetamide-Based Inhibitors of Na Pump (ATP4) with Fast-Killing Asexual Blood-Stage Antimalarial Activity by Phenotypic Screening.
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 PDFTandem Mass Spectrometry and Bio-Guided Isolation of Secondary Metabolites With Antiplasmodial Activity From Dalbergia miscolobium Bark.
Chem 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 PDFComputational investigation of mutations in PfCRT and PfDHFR proteins for emerging resistance of Plasmodium falciparum to antimalarial drugs.
Mol 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 PDFDesign, Synthesis, and Evaluation of Triazolyl Quinoline Derivatives as Potential Antimalarial Agents.
Chem 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 PDFNatural Products, Synthesis, and Biological Activities of Quinolines (2020-2024).
Mini 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.
View Article and Find Full Text PDF