In vitro assessment of 3-alkoxy-5-nitroindazole-derived ethylamines and related compounds as potential antileishmanial drugs.

Leishmaniasis is a widespread neglected tropical disease complex that is responsible of one million new cases per year. Current treatments are outdated and pose many problems that new drugs need to overcome. With the goal of developing new, safe, and affordable drugs, we have studied the in vitro activity of 12 different 5-nitroindazole derivatives that showed previous activity against different strains of Trypanosoma cruzi in a previous work. T. cruzi belongs to the same family as Leishmania spp., and treatments for the disease it produces also needs renewal. Among the derivatives tested, compounds 1, 2, 9, 10, 11, and 12 showed low J774.2 macrophage toxicity, while their effect against both intracellular and extracellular forms of the studied parasites was higher than the ones found for the reference drug Meglumine Antimoniate (Glucantime®). In addition, their Fe-SOD inhibitory effect, the infection rates, metabolite alteration, and mitochondrial membrane potential of the parasites treated with the selected drugs were studied in order to gain insights into the action mechanism, and the results of these tests were more promising than those found with glucantime, as the leishmanicidal effect of these new drug candidates was higher. The promising results are encouraging to test these derivatives in more complex studies, such as in vivo studies and other experiments that could find out the exact mechanism of action.

Gap Analysis of the Habitat Interface of Ticks and Wildlife in Mexico.

Mexico is a highly diverse country where ticks and tick-borne diseases (TBD) directly impact the health of humans and domestic and wild animals. Ticks of the genera Rhipicephalus spp., Amblyomma spp., and Ixodes spp. represent the most important species in terms of host parasitism and geographical distribution in the country, although information on other genera is either limited or null. In addition, information regarding the influence of global warming on the increase in tick populations is scarce or nonexistent, despite climate conditions being the most important factors that determine tick distribution. In order to aid in the management of ticks and the risks of TBD in humans and domestic animals in Mexico, an analysis was conducted of the gaps in information on ticks with the purpose of updating the available knowledge of these ectoparasites and adapting the existing diagnostic tools for potential distribution analysis of TBD in wildlife. These tools will help to determine the epidemiological role of wildlife in the human-domestic animal interface in anthropized environments in Mexico.

Presence of trypanosomatid antibodies in gray foxes (Urocyon cinereoargenteus) and domestic and feral dogs (Canis lupus familiaris) in Queretaro, Mexico.

Trypanosoma cruzi and Leishmania spp. are vector-borne parasitic protozoa, the causative agents of Chagas and Leishmaniasis diseases, respectively. Trypanosoma cruzi and Leishmania spp. have been reported in a wide variety of mammals, including canids, which play an important role in the transmission of these parasites between urban and natural environments. Currently, no studies have been conducted on trypanosomatids in wild canids in Mexico. Using a partially purified fraction of excreted Iron Superoxide dismutase (FeSODe) of T. cruzi, L. mexicana, and L. infantum as antigen for the ELISA and Western blot tests, we detected the presence of antibodies against these parasites in gray foxes (Urocyon cinereoargenteus Schreber, 1775), domestic and feral dogs (Canis lupus familiaris L.) from Queretaro. Our study provides new information regarding the potential of these carnivores as reservoirs of T. cruzi, Leishmania mexicana, and L. infantum for Latin America.

Gray fox (Urocyon cinereoargenteus) parasite diversity in central Mexico.

Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775) and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC) were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico) Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013-2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species), mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission.

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives.

Chagas disease is a neglected tropical disease with 6-7 million people infected worldwide, and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity, and a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7, and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high antiparasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent.