This study explores the synthesis and evaluation of novel 1,2,3-triazole-methyl-1,4-naphthoquinone hybrids, focusing on their electrochemical properties and antiparasitic efficacies against two human blood-dwelling parasites Plasmodium falciparum and Schistosoma mansoni. Using copper-catalyzed azide-alkyne cycloaddition (CuAAC), a well-established tool in click chemistry, two synthetic routes were assessed to develop α- and β-[triazole-methyl]-menadione derivatives. By optimizing the CuAAC reaction conditions, yields were significantly improved, reaching up to 94 % for key intermediates and resulting in the formation of a library of approximately 30 compounds.
View Article and Find Full Text PDFThe development of redox-sensitive molecular fluorescent probes for the detection of redox changes in Plasmodium falciparum-parasitized red blood cells remains of interest due to the limitations of current genetically encoded biosensors. This study describes the design, screening and synthesis of new pro-fluorophores based on flavylium azido dyes coupled by CuAAC click chemistry to alkynyl analogues of plasmodione oxide, the key metabolite of the potent redox-active antimalarial plasmodione. The photophysical and electrochemical properties of these probes were evaluated, focusing on their fluorogenic responses.
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November 2024
Ψ-1,4-naphthoquinones (Ψ-NQ) are non-quinoid compounds in which aromaticity-found in 1,4-naphthoquinones-is broken by the introduction of an angular methyl at C-4a or -8a. This series was designed to act as prodrugs of 1,4-naphthoquinones in an oxidative environment. Furthermore, from a medicinal chemistry point of view, the loss of planarity of the scaffold might lead to an improved solubility and circumvent the bad reputation of quinones in the pharmaceutical industry.
View Article and Find Full Text PDFThe apicoplast is an essential organelle for the viability of apicomplexan parasites or , which has been proposed as a suitable drug target for the development of new antiplasmodial drug-candidates. Plasmodione, an antimalarial redox-active lead drug is active at low nM concentrations on several blood stages of such as early rings and gametocytes. Nevertheless, its precise biological targets remain unknown.
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