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Effective anti-leishmanial activity of minimalist squaramide-based compounds

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dc.contributor.author Marín, Clotilde
dc.contributor.author Ximenis Campins, Marta
dc.contributor.author Ramirez-Macías, Inmaculada
dc.contributor.author Rotger Pons, María del Carmen
dc.contributor.author Urbanova, Kristina
dc.contributor.author Olmo, Francisco
dc.contributor.author Martín-Escolano, Rubén
dc.contributor.author Rosales, María José
dc.contributor.author Cañas, Rocío
dc.contributor.author Gutierrez-Sánchez, Ramón
dc.contributor.author Costa Torres, Antonio
dc.contributor.author Sánchez-Moreno, Antonio
dc.date.accessioned 2018-10-15T11:13:55Z
dc.identifier.uri http://hdl.handle.net/11201/148054
dc.description.abstract [eng] In order to evaluate the in vitro leishmanicidal activity of N,N0-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by 1H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)- 4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Experimental Parasitology, 2016, vol. 170, p. 36-49
dc.title Effective anti-leishmanial activity of minimalist squaramide-based compounds
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2018-10-15T11:13:55Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess


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