Heterocyclic Diamines with Leishmanicidal Activity
journal contributionposted on 2021-11-04, 15:03 authored by Álvaro Martín-Montes, María Paz Clares, Rubén Martín-Escolano, Estefanía Delgado-Pinar, Clotilde Marín, Begoña Verdejo, Álvaro Martínez-Camarena, Daniel Molina-Carreño, Enrique García-España, Manuel Sánchez-Moreno
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 There are no effective human vaccines for its prevention, and outdated drugs hamper treatment.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 IC25 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.
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parasite infectivity ratesleishmanicidal activity leishmaniasisleishmaniasis chemotherapy duefight leishmaniasis remainseffective human vaccinescrucial goal today12 million peopleleishmania infantum </leishmania donovani </leishmania braziliensis </reference drug glucantime25 </ subthree derivatives affectedleishmania </worldwide prevalenceworld ’vivo efficacyshowing alterationsresearch aimedready synthesisquinoline heterocyclespotential candidatesneglected diseasesmolecules couldheterocyclic diaminesgreater levelsglucose catabolismglucantime testedamastigote formsamastigote form