Targeting with structural analogs of natural products the purine salvage pathway in Leishmania (Leishmania) infantum by computer-aided drug-design approaches

Página do item simplificado
dc.creatorHaruna Luz Barazorda-Ccahuana
dc.creatorEymi Gladys Cárcamo-Rodriguez
dc.creatorAngela Emperatriz Centeno-Lopez
dc.creatorAlexsandro Sobreira Galdino
dc.creatorRicardo Andrez Machado-de-Ávila
dc.creatorRodolfo Cordeiro Giunchetti
dc.creatorEduardo Antonio Ferraz Coelho
dc.creatorMiguel Angel Chávez-Fumagalli
dc.date.accessioned2026-01-12T23:12:57Z
dc.date.issued2024-02-03
dc.identifier.doihttps://doi.org/10.3390/tropicalmed9020041
dc.identifier.issn2414-6366
dc.identifier.urihttps://hdl.handle.net/1843/1370
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofTropical medicine and infectious disease
dc.rightsAcesso aberto
dc.subjectLeishmania infantum
dc.subject.otherDrug discovery
dc.subject.otherNatural products
dc.subject.otherSkimmianine
dc.subject.otherVisceral Leishmaniasis
dc.subject.otherMolecular docking simulation
dc.subject.otherMolecular dynamics simulation
dc.subject.otherVirtual screening
dc.titleTargeting with structural analogs of natural products the purine salvage pathway in Leishmania (Leishmania) infantum by computer-aided drug-design approaches
dc.typeArtigo de periódico
local.citation.epage17
local.citation.issue2
local.citation.spage1
local.citation.volume9
local.description.resumoVisceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future.
local.identifier.orcidhttps://orcid.org/0000-0001-8791-0506
local.identifier.orcidhttps://orcid.org/0000-0002-9368-0329
local.identifier.orcidhttps://orcid.org/0000-0002-8670-963X
local.identifier.orcidhttps://orcid.org/0000-0002-8890-3030
local.identifier.orcidhttps://orcid.org/0000-0002-1303-0490
local.identifier.orcidhttps://orcid.org/0000-0003-4181-7546
local.identifier.orcidhttps://orcid.org/0000-0002-3991-9343
local.identifier.orcidhttps://orcid.org/0000-0002-8394-4802
local.publisher.countryBrasil
local.publisher.departmentMEDICINA - FACULDADE DE MEDICINA
local.publisher.initialsUFMG
local.subject.cnpqCIENCIAS DA SAUDE
local.url.externahttps://www.mdpi.com/2414-6366/9/2/41

Arquivos

Pacote original

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
Targeting with structural analogs of natural products the purine salvage pathway in Leishmania (Leishmania) infantum by computer-aided drug-design approaches.pdf
Tamanho:
9.39 MB
Formato:
Adobe Portable Document Format
Baixar

Licença do pacote

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
license.txt
Tamanho:
2.07 KB
Formato:
Item-specific license agreed to upon submission
Descrição:
Baixar

Coleções

Artigo de Periódico

Logo UFMG