The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001) against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC) were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol). The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2) and a human cell line (WI-26VA4). Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM) and inactive against WI-26VA4 (IC50 > 200 µM). Further ligand optimisation cycles generated new prospects for docking and biological assays.

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Introdução: Os mosquitos vetores de doenças são um problema de saúde pública em todo o mundo. Entretanto, controlar esses insetos é um desafio,  e assim os inseticidas naturais são uma estratégia promissora devido seu potencial e baixa toxicidade. O neem (Azadiractha indica A. Juss, Meliaceae) é uma árvore que possui vários compostos bioativos e um amplo espectro de ação, incluindo repelência e larvicida.  Objetivos: Esta revisão tem como objetivo mostrar o uso de produtos à base de Neem usados contra vetores de doenças. Metodologia: Vários artigos foram analisados e mostraram que diferentes compostos derivados estão sendo avaliados, como extratos, óleos, bolo de neem (subproduto da extração), além de nanopartículas sintetizadas. Resultados: Com base nos resultados, fornecemos uma lista de compostos avaliados que mostraram ser variáveis em relação aos valores de CL50 em relação a três espécies de mosquitos (Culex quinquefasciatus, Anopheles stephensi e Aedes aegypti). Conclusão: Comprovamos a relevância médica desta árvore no combate a estes vetores de doenças.

Four novel Cr (III), Co (II) and Ni (II) complexes with 2-thiazoline-2-tiol derivative ligands were synthesized and characterized using elemental, physiochemical, and spectroscopy analytical methods. the results showed the formation of ligands coordinated by sulfur atoms of the C = S bond to the l1 ligand and by the sulfur atom of the C-S bond and/or nitrogen of the intra C-ring bond of the l2 ligand. the activity of the complexes against Gram-negative, Gram-positive bacteria and yeasts of clinical importance was evaluated by broth microdilution method. the best result was obtained to l2-Ni compound against E. cloacae (Minimal Inhibitory Concentration (MIC) = 62.5 µg/ml). Additionally, the compounds showed anti-Candida activity (MIC values ranging from 250 to 500 µg/ml), except the l1-Cr that was not active against any tested microorganism.

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