Malaria still affects around 200 million people and is responsible for more than 400,000 deaths per year, mostly children in subequatorial areas. This disease is caused by parasites of the genus. Only a few WHO-recommended treatments are available to prevent or cure plasmodial infections, but genetic mutations in the causal parasites have led to onset of resistance against all commercial antimalarial drugs. New drugs and targets are being investigated to cope with this emerging problem, including enzymes belonging to the main metabolic pathways, while nucleoside and nucleotide analogues are also a promising class of potential drugs. This review highlights the main metabolic pathways targeted for the development of potential antiplasmodial therapies based on nucleos(t)ide analogues, as well as the different series of purine-containing nucleoside and nucleotide derivatives designed to inhibit purine metabolism.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00182 | DOI Listing |
Nucleosides Nucleotides Nucleic Acids
January 2025
Department of PG Studies and Research in Environmental Science, Kuvempu University, Shankaraghatta, India.
This article presents a new and facile method for the synthesis of Schiff base compounds with a benzimidazole group using a low-cost and reusable calcium aluminate nanophosphorus catalyst (CaAlO). This approach avoids harmful solvents and reactants, supporting a more environmentally friendly synthesis process. The catalyst maintained its activity and heterogeneity over four cycles with minimal loss of efficiency.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites.
View Article and Find Full Text PDFPlant Physiol
January 2025
Leibniz Universität Hannover, Department of Molecular Nutrition and Biochemistry of Plants, Herrenhäuser Str. 2, 30419 Hannover, Germany.
The vacuole is an important site for RNA degradation. Autophagy delivers RNA to the vacuole, where the vacuolar T2 RNase Ribonuclease 2 (RNS2) plays a major role in RNA catabolism. The presumed products of RNS2 activity are 3'-nucleoside monophosphates (3'-NMPs).
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
January 2025
Department of Veterinary Genetics, Faculty of Veterinary, Ondokuz Mayıs University, Samsun, Turkey.
Objective: Type 2 Diabetes Mellitus (T2DM) can lead to long-term vascular complications such as diabetic peripheral neuropathy (DPN). This study aimed to investigate the role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and angiotensin II type 1 receptor (AT1R) A1166C variants in the predisposition to T2DM in the Turkish population and their association with DPN.
Methods: The study included 90 T2DM patients (42 with DPN) and 50 healthy individuals.
NPJ Regen Med
January 2025
Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity.
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