In vivo evaluation of anti-leishmania activity of alkyltriazoles and alkylphosphocholines by oral route

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dc.creatorVanessa Silva Gontijo
dc.creatorFábio Antônio Colombo
dc.creatorPatrícia Ferreira Espuri
dc.creatorPoliany Graziella de Freitas
dc.creatorJuliana Barbosa Nunes
dc.creatorLevy Bueno Alves
dc.creatorMárcia Paranho Veloso
dc.creatorRosemeire Brondi Alves
dc.creatorRossimiriam Pereira de Freitas
dc.creatorMarcos José Marques
dc.date.accessioned2024-08-05T16:03:51Z
dc.date.accessioned2025-09-09T01:14:30Z
dc.date.available2024-08-05T16:03:51Z
dc.date.issued2021
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.exppara.2021.108123
dc.identifier.issn1090-2449
dc.identifier.urihttps://hdl.handle.net/1843/72590
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofExperimental Parasitology
dc.rightsAcesso Aberto
dc.subjectQuímica farmacêutica
dc.subjectLeishmaniose visceral
dc.subject.otherVisceral leishmaniasis
dc.subject.otherIn vivo activity
dc.subject.otherAlkylphosphocholine
dc.subject.otherAlkyltriazole
dc.subject.otherqPCR
dc.subject.otherMolecular docking
dc.titleIn vivo evaluation of anti-leishmania activity of alkyltriazoles and alkylphosphocholines by oral route
dc.typeArtigo de periódico
local.citation.spage108123
local.citation.volume226-227
local.description.resumoThe failures in the treatment of leishmaniasis is an increasing problem around the world, especially related to resistance. Thus, we describe the synthesis and in vivo anti-Leishmania activity of alkylphosphocholine and alkyltriazoles; besides, their likely action mechanisms stem from some eventual inhibition of parasite enzymes using computational tools. These compounds were tested in an in vivo hamster model infected with Leishmania Leishmania infantum chagasi. Fifty days after parasite inoculation, the two compounds 12-azidedodecylphosphocholine (3) and 3-(1-(12-fluorododecyl)-1H-1,2,3-triazol-1-yl)propano-1-ol (9), were separately administered once a day as oral suspensions (25 and 12.5 mg/kg/day, respectively) during ten days, and their efficacy was compared to the reference compound pentavalent antimonial Glucantime (GLU). Compound 3 significantly reduced the number of parasites in the spleen (4.93 × 102 amastigotes/g) and liver (4.52 × 103 amastigotes/g). Compound 9 reduced the number of amastigotes in the spleen to 1.30 × 104 and 1.36 × 103 amastigotes/g in the liver. GLU was the most effective overall treatment (7.50 × 101 and 2.28 × 102 amastigotes/g in the spleen and liver, respectively). The high activity levels of these compounds in vivo may stem from their high in vitro leishmanicidal activity and lipophilicity. The in silico absorption, distribution, metabolism, and excretion studies also showed some anti-Leishmania potential. Compound 9 had more lipophilic characteristics than those of compound 3. In silico studies of the nine enzymes of compounds 3 and 9 showed significant evidence of interactions with nicotimidase and tyrosine aminotransferase, demonstrating possible inhibition enzymes present in L. (L.) infantum chagasi. These compounds could be a promising template for developing a new class of leishmanicidal agents, by oral route, and deserve further investigation to explore different therapeutic regimens.
local.identifier.orcidhttps://orcid.org/0000-0003-1674-818X
local.identifier.orcidhttps://orcid.org/0000-0002-1596-9709
local.identifier.orcidhttps://orcid.org/0000-0002-1403-0249
local.identifier.orcidhttps://orcid.org/0000-0003-2628-0357
local.identifier.orcidhttps://orcid.org/0000-0002-0223-8982
local.identifier.orcidhttps://orcid.org/0000-0003-0546-2549
local.identifier.orcidhttps://orcid.org/0000-0001-6974-3724
local.identifier.orcidhttps://orcid.org/0000-0003-3459-3169
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0014489421000606

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