Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus . This is due to a single amino acid change within the target of PZQ, a transient receptor potential ion channel (TRPM), in species. Here we identify benzamidoquinazolinone analogs that are active against TRPM. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and damage to the protective tegument of these liver flukes. BZQ also retained activity against comparable to PZQ and was active against TRPM orthologs in all profiled species of parasitic fluke. This broad spectrum activity was manifest as BZQ adopts a pose within the binding pocket of TRPM dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPM and a first-in-class, broad spectrum flukicide.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542552 | PMC |
| http://dx.doi.org/10.1101/2023.09.22.559026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Production, Delivery, and Regulatory Aspects for Application of Plant-Based Anti-microbial Peptides: a Comprehensive Review.
Probiotics Antimicrob Proteins
January 2025
Faculty of Biotechnologies (BioTech), ITMO University, 9 Lomonosova Street, 191002, Saint Petersburg, Russia.
Antimicrobial peptides (AMPs) are small, positively charged biomolecules produced by various organisms such as animals, microbes, and plants. These AMPs play a significant role in defense mechanisms and protect from adverse conditions. The emerging problem of drug resistance in microbes poses a global health challenge in treating diseases.
View Article and Find Full Text PDFUnveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations.
Nat Prod Bioprospect
January 2025
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
In the twenty-first century, we have witnessed multiple coronavirus pandemics. Despite declining SARS-CoV-2 cases, continued research remains vital. We report the discovery of sydowiol B, a natural product, as a dual inhibitor of SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro).
View Article and Find Full Text PDFCybertoxicology, molecular docking, and experimental verification reveal the mechanism of action of chlorpyrifos on skin damage.
Ecotoxicol Environ Saf
January 2025
Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Research Institute of Orthopedics, the Jiangnan Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address:
Chlorpyrifos (CPF) is a broad-spectrum organophosphate chloride (OP) insecticide widely used in domestic use and open field. However, there is currently no relevant research revealing the toxic effects of CPF exposure on the skin, then it is necessary to comprehensively understand the toxic effects and mechanisms. The results showed that the skin tissue structure and function of mice were significantly disrupted after CPF exposure.
View Article and Find Full Text PDFA competitive dual-mode for tetracycline antibiotics sensing based on colorimetry and surface-enhanced Raman scattering.
Biosens Bioelectron
December 2024
State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, People's Republic of China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 214122, Wuxi, Jiangsu, People's Republic of China; International Joint Laboratory on Food Safety, Jiangnan University, 214122, Wuxi, Jiangsu, People's Republic of China. Electronic address:
Tetracycline antibiotics (TCs) are extensively used as broad-spectrum antimicrobials. However, their excessive use and misuse have led to serious accumulation in foods and environments, posing a significant threat to human health. To solve such public issue, we have designed a novel dual-mode detection method, integrating colorimetric sensing with surface-enhanced Raman scattering (SERS) technology, for sensitive and rapid evaluation on TCs.
View Article and Find Full Text PDFPoint prevalence survey of antibiotic use in Mexican secondary care hospitals.
PLoS One
January 2025
National Institute of Public Health of Mexico, Center for Evaluation and Surveys Research, Cuernavaca, Morelos, Mexico.
Introduction: Tackling the inertia of growing threat of antimicrobial resistance (AMR) requires changes in how antibiotics are prescribed and utilized. The monitoring of antimicrobial prescribing in hospitals is a critical component in optimizing antibiotic use. Point prevalence surveys (PPSs) enable the surveillance of antibiotic prescribing at the patient level in small hospitals that lack the resources to establish antimicrobial stewardship programs (ASP).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!