Targeting Cysteine Protease B to Discover Antileishmanial Drugs: Directions and Advances

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117500 - 117500

Published: March 11, 2025

Language: Английский

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Recent Progress in Thiazole, Thiosemicarbazone, and Semicarbazone Derivatives as Antiparasitic Agents Against Trypanosomatids and Plasmodium spp.

Molecules, Journal Year: 2025, Volume and Issue: 30(8), P. 1788 - 1788

Published: April 16, 2025

Neglected tropical diseases (NTDs), including Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria, remain a major global health challenge, disproportionately affecting low-income populations. Current therapies for these suffer from significant limitations, such as reduced efficacy, high toxicity, emerging parasite resistance, highlighting the urgent need new therapeutic strategies. In response, substantial efforts have been directed toward synthesis of molecules with improved potency, selectivity, pharmacokinetic profiles. However, despite many compounds exhibiting favorable ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles strong in vitro activity, their translation into vivo models remains limited. Key challenges include lack investment, absence fully representative experimental models, difficulties extrapolating cell-based assay results to more complex biological systems. this review, we analyzed latest advancements (2019–2024) development compound classes, correlating predictive parameters observed activity. Among parameters, highlighted partition coefficient (LogP), which measures compound’s lipophilicity influences its ability cross membranes, Caco-2 cell permeability, an model widely used predict intestinal drug absorption. Additionally, prioritized most promising structural classes pharmaceutical development, discussing structure–activity relationships (SARs) remaining that must be overcome enable clinical application treatment NTDs.

Language: Английский

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Enhancing Antileishmanial Activity of Amidoxime-Based Compounds Bearing a 4,5-Dihydrofuran Scaffold: In Vitro Screening Against Leishmania amazonensis

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5469 - 5469

Published: Nov. 20, 2024

Leishmaniasis, a protozoan disease affecting humans, exposes significant shortcomings in current treatments. In continuation to our previous findings on amidoxime-based antileishmanial compounds bearing 4,5-dihydrofuran scaffold, twelve new amidoxime derivatives substituted at position 3 with an amide nitrogen heterocycle were synthesized. This series was designed replace the sulfone and aryl group previously reported HIT. The synthesis of these involved following three-step pathway: manganese (III) acetate-based cyclization β-ketoester, followed by amidation LiHMDS final reaction hydroxylamine. Three them, containing either bromine, chlorine, or methyl substitutions featuring pyridine moiety, showed interesting toxicity-activity relationship vitro. They exhibited IC

Language: Английский

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Antileishmanial potential of thiourea-based derivatives: design, synthesis and biological activity

RSC Advances, Journal Year: 2024, Volume and Issue: 14(50), P. 37131 - 37141

Published: Jan. 1, 2024

The evaluation of the results showed that compounds 4g and 20a–b could be promising leads/hits to enrich arsenal antileishmanial drug development.

Language: Английский

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