The aim of this research is to identify potential candidate molecules against Leishmania mexicana, a local pathogen causative of leishmaniasis. Leishmaniasis is a neglected tropical disease that poses a significant public health challenge in the Americas due to its high incidence, morbidity, widespread geographic presence, diverse parasite species, various clinical manifestations, and the absence of adequate therapeutic and preventative measures. L. mexicana is the causative agent of cutaneous leishmaniasis in Mexico and Central America. Ecuador is an endemic area for cutaneous leishmaniasis with around 1200 annual cases. Many of the drugs used to treat leishmaniasis are from the early and mid-20th centuries, have limited efficacy in advanced stages of the disease, are nonspecific, and/or are highly toxic. Finding new starting points for developing new drugs to effectively treat and control these diseases is therefore a priority.

The current increase in microbial resistance is a very serious public health problem that requires immediate attention from the scientific-multidisciplinary sector and is supported by the corresponding socio-political commitment. Here we screen, through in silico methods, pre-synthesized compounds provided by Medicines for Malaria Venture (MMV) in the Pandemic Response box (PRB) (www.mmv.org). PRB is a collection of 400 compounds to facilitate drug discovery (Samby et al., 2022). The collection contains chemically characterized compounds that are freely available to the scientific community, with the understanding that the data will be shared. Here we assess the antimicrobial potential of the novel compounds against topoisomerases type II of L. mexicana by molecular docking. This pathogen has one Topo II located in the nucleus and another located in the mitochondria. These enzymes are essential for the parasite´s survival. We identified the 20 best candidates for both enzymes being 5 of the themes shared by both targets. These promising antimicrobial molecules will be tested in vitro against eukaryotic macrophages and leishmania models (promastigotes and amastigotes), to validate their effectivity.