Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria.
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http://dx.doi.org/10.2174/1389203717999160226180353 | DOI Listing |
Phys Sportsmed
January 2025
Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, Serbia.
Purpose: This systematic review aims to synthesize the current research on doping in combat sports, examining the prevalence, detection methods, prevention strategies, and overall impact on combat sports.
Design/methodology/approach: Of the 21 identified articles, six met the inclusion criteria. A systematic approach was used, including content analysis based on specific criteria: articles in English, original research, and relevance to sport and doping.
J Med Chem
January 2025
The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China.
CDK4/6 inhibitors are effective in treating HR/HER2 breast cancer but face limitations due to therapeutic resistance and hematological toxicity, particularly from strong CDK6 inhibition. To address these challenges, designing selective inhibitors targeting specific cyclin-dependent kinases (CDK) members could offer clinical advantages and broaden CDK inhibitor indications. However, the highly conserved binding pockets of CDKs complicate selective targeting.
View Article and Find Full Text PDFNat Prod Res
January 2025
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
The chloroform extract of leaves of L, reduced the levels of lipid profile in rats with hypercholesterolaemia to near-normal levels. Additionally, it significantly decreased the amount of malondialdehyde (MDA). In addition, the extract augmented the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) in the hypercholesterolemic treated rats.
View Article and Find Full Text PDFInt J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
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