In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared, 1H, 13C, and 31P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC50 values of 6.44 ± 1.49 and 12.25 ± 0.68 µM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.

Este artigo descreve a síntese e a atividade antileishmania de novos derivados pirazolil benzenossulfonamídicos. Estes foram elucidados por métodos espectrométricos. Alguns compostos mostraram uma atividade in vitro significativa contra Leishmania amazonensis, destacando-se o derivado 1e. Nenhum dos derivados pirazolil benzenossulfonamídicos mostraram qualquer toxicidade em macrófagos murinos.

This paper describes the synthesis and the antileishmanial activity of new pyrazolyl benzenesulfonamide derivatives. These were elucidated by spectrometric methods. Some compounds showed a significant in vitro activity against Leishmania amazonensis, highlighting the derivative 1e. These pyrazolyl benzenesulfonamide derivatives did not show any toxicity in murine macrophage.

Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)50 = 2 µM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 µM) and La10 (IC50 = 10 µM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance.

The isolation of bioactive compounds from medicinal plants, based on traditional use or ethnomedical data, is a highly promising potential approach for identifying new and effective antimalarial drug candidates. The purpose of this review was to create a compilation of the phytochemical studies on medicinal plants used to treat malaria in traditional medicine from the Community of Portuguese-Speaking Countries (CPSC): Angola, Brazil, Cape Verde, Guinea-Bissau, Mozambique and São Tomé and Príncipe. In addition, this review aimed to show that there are several medicinal plants popularly used in these countries for which few scientific studies are available. The primary approach compared the antimalarial activity of native species used in each country with its extracts, fractions and isolated substances. In this context, data shown here could be a tool to help researchers from these regions establish a scientific and technical network on the subject for the CPSC where malaria is a public health problem.

A quimioterapia para as leishmanioses, doenças causadas por protozoários do gênero Leishmania, ainda permanece ineficiente em diversos tratamentos. Portanto, existe a necessidade de pesquisa por novos fármacos. Nesse trabalho, foram sintetizados derivados 1-aril-1H-pirazol-4-carboximidamidas, avaliadas as atividades leishmanicida e os efeitos citotóxicos in vitro, e realizado um estudo de relação estrutura-atividade (REA) com a série de compostos. O composto 2 apresentou um perfil de atividade que pode ser melhorado através de estratégias de modificação molecular da química medicinal.

Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies.

The direct agglutination test (DAT) based on a freeze-dried antigen and the rK39 dipstick test were evaluated for the sero-diagnosis of visceral leishmaniasis (VL). The sensitivity and specificity of both tests were determined using sera from confirmed VL patients (n = 21), healthy controls (n = 19) and from patients with other confirmed infectious diseases (n = 42). The DAT had a sensitivity and a specificity of 100%. The rK39 had a sensitivity of 85.7% and a specificity of 82%. Both tests were also used to screen blood samples of confirmed VL patients (n = 15) and serum samples of VL suspects (n = 61). The DAT found all blood samples of confirmed VL patients positive and tested 98.4% of the serum samples of the VL suspects positive. In contrast, rK39 detected in 9/15 blood samples (60%) antibodies against Leishmania chagasi and found 85.3% of the serum samples of the suspected patients positive. Although the rK39 dipstick is more rapid and user friendlier than the DAT, the latter has a superior sensitivity and specificity. Furthermore, the reagents used for DAT do not require cold storage, whereas the buffer of the rK39 must be stored at 4ºC. Therefore, the DAT is the most suitable test for the sero-diagnosis of VL under field conditions.