Synthesis of 1,2,3-Triazole-Methyl-Menadione Derivatives: Evaluation of Electrochemical and Antiparasitic Properties against two Blood-Dwelling Parasites.

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.

Click Coupling of Flavylium Dyes with Plasmodione Analogues: Towards New Redox-Sensitive Pro-Fluorophores.

The 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.

Regioselective Synthesis of Potential Non-Quinonoid Prodrugs of Plasmodione: Antiparasitic Properties Against Two Hemoglobin-Feeding Parasites and Drug Metabolism Studies.

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.

3-Benzylmenadiones and their Heteroaromatic Analogues Target the Apicoplast of Apicomplexa Parasites: Synthesis and Bioimaging Studies.

The 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.