Leishmaniasis is one of the world's most neglected diseases with a worldwide prevalence of 12 million people. There are no effective human vaccines for its prevention, and outdated drugs hamper treatment. Therefore, research aimed at developing new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, here, we present 10 new compounds made up by linking alkylated ethylenediamine units to pyridine or quinoline heterocycles with promising in vitro and in vivo efficacy against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani, and Leishmania braziliensis species. Three compounds (2, 4, and 5) showed a selectivity index much higher in the amastigote form than the reference drug glucantime. These three derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC 25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing alterations in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy due to their effectiveness and their ready synthesis.
Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.
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