Browsing by Author "Muskus, Carlos"
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Item Identificación molecular de aislamientos clínicos de Leishmania spp. procedentes de Colombia con base en el gen hsp70(Biomedica : revista del Instituto Nacional de Salud, 2016) Montalvo, Ana M.; Fraga, Jorge; Montano, Ivón; Lianet, Monzote; Gert Van, der Auwera; Marín, Marcel; Muskus, CarlosLa leishmaniasis es una enfermedad de gran prevalencia en Colombia, donde al menos seis especies diferentes la originan en el ser humano, con un amplio rango de características clínicas. La tipificación de la especie es importante, no solo desde el punto de vista epidemiológico, sino para el diagnóstico, dado que el tratamiento puede variar dependiendo de la especie identificada. En la identificación se han utilizado varias alternativas metodológicas con diferentes niveles de poder discriminatorio.Item Identification of potential kinase inhibitors within the pi3k/akt pathway of leishmania species(2021) Ochoa, Rodrigo; Ortega Pajares, Amaya; Castello, Florencia A.; Serral, Federico; Fernández Do Porto, Darío; Villa Pulgarin, Janny A.; Varela M, Rubén E.; Muskus, CarlosLeishmaniasis is a public health disease that requires the development of more effective treatments and the identification of novel molecular targets. Since blocking the PI3K/AKT pathway has been successfully studied as an effective anticancer strategy for decades, we examined whether the same approach would also be feasible in Leishmania due to their high amount and diverse set of annotated proteins. Here, we used a best reciprocal hits protocol to identify potential protein kinase homologues in an annotated human PI3K/AKT pathway. We calculated their ligandibility based on available bioactivity data of the reported homologues and modelled their 3D structures to estimate the druggability of their binding pockets. The models were used to run a virtual screening method with molecular docking. We found and studied five protein kinases in five different Leishmania species, which are AKT, CDK, AMPK, mTOR and GSK3 homologues from the studied pathways. The compounds found for different enzymes and species were analysed and suggested as starting point scaffolds for the design of inhibitors. We studied the kinases’ participation in protein–protein interaction networks, and the potential deleterious effects, if inhibited, were supported with the literature. In the case of Leishmania GSK3, an inhibitor of its human counterpart, prioritized by our method, was validated in vitro to test its anti-Leishmania activity and indirectly infer the presence of the enzyme in the parasite. The analysis contributes to improving the knowledge about the presence of similar signalling pathways in Leishmania, as well as the discovery of compounds acting against any of these kinases as potential molecular targets in the parasite