In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis

dc.creatorSilva, Dahara Keyse Carvalho
dc.creatorTeixeira, Jessicada Silva
dc.creatorMoreira, Diogo Rodrigo Magalhães
dc.creatorSilva, Tiago Fernandes da
dc.creatorBarreiro, Eliezer Jesus de Lacerda
dc.creatorFreitas, Humberto Fonseca de
dc.creatorPita, Samuel Silva da Rocha
dc.creatorTeles, André Lacerda Braga
dc.creatorGuimarães, Elisalva Teixeira
dc.creatorSoares, Milena Botelho Pereira
dc.date2021-02-16T13:24:54Z
dc.date2021-02-16T13:24:54Z
dc.date2020
dc.date.accessioned2023-09-26T23:13:23Z
dc.date.available2023-09-26T23:13:23Z
dc.identifierSILVA, Dahara Keyse Carvalho et al. In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis. Frontiers in Pharmacology, v. 11, p. 1-14, 2020.
dc.identifier1663-9812
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/46085
dc.identifier10.3389/fphar.2020.590544
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8888193
dc.descriptionInstitutional Animal Care and Use Committee, Ethics Committee for Animal Experimentation of FIOCRUZ (CEUA/FIOCRUZ Permit Number: L-IGM-004/2019).
dc.descriptionLeishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an N-acylhydrazone derivative. Here we investigated the in vitro and in vivo activity of LASSBio-1386 against L. amazonensis. LASSBio-1386 inhibited the proliferation of promastigotes of L. amazonensis (EC50 2.4 ± 0.48 μM), while presenting low cytotoxicity to macrophages (CC50 74.1 ± 2.9 μM). In vitro incubation with LASSBio- 1386 reduced the percentage of Leishmania-infected macrophages and the number of intracellular parasites (EC50 9.42 ± 0.64 μM). Also, in vivo treatment of BALB/c mice infected with L. amazonensis resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of L. amazonensis. Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on Leishmania phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against Leishmania through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectLeishmania
dc.subjectDoenças Negligenciadas
dc.subjectTratamento
dc.subjectMacrófagos
dc.subjectFosfodiesterase
dc.subjectLeishmania amazonensis
dc.subjectLASSBio-1386
dc.subjectTreatment
dc.subjectN-acyl hydrazones
dc.subjectPhosphodiesterase
dc.titleIn Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis
dc.typeArticle


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