Revealing the binding process of new 3-alkylpyridine marine alkaloid analogue antimalarials and the heme group: an experimental and theoretical investigation

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dc.creatorRenato Márcio Ribeiro Viana
dc.creatorAnna Paola Butera
dc.creatorEliziane da Silva Santos
dc.creatorCésar Augusto Tischer
dc.creatorRosemeire Brondi Alves
dc.creatorRossimiriam Pereira de Freitas
dc.creatorLuciana Guimarães
dc.creatorFernando de Pilla Varotti
dc.creatorGustavo Henrique Ribeiro Viana
dc.creatorClebio Soares Nascimento Junior
dc.date.accessioned2024-08-01T13:12:01Z
dc.date.accessioned2025-09-08T22:49:47Z
dc.date.available2024-08-01T13:12:01Z
dc.date.issued2016
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.description.sponsorshipFINEP - Financiadora de Estudos e Projetos, Financiadora de Estudos e Projetos
dc.identifier.doihttps://doi.org/10.1021/acs.jcim.5b00742
dc.identifier.issn1549-960X
dc.identifier.urihttps://hdl.handle.net/1843/72256
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of Chemical Information and Modeling
dc.rightsAcesso Restrito
dc.subjectAgentes antiinfecciosos
dc.subjectQuímica bioinorgânica
dc.subjectLigantes (Bioquímica)
dc.subjectAlcalóides
dc.subjectPlasmodium falciparum
dc.subjectMalária
dc.subjectEspectrometria de massa
dc.subject.otherAntimicrobial agents
dc.subject.otherBioinorganic chemistry
dc.subject.otherLigands
dc.subject.otherMathematical methods
dc.subject.otherParasites
dc.titleRevealing the binding process of new 3-alkylpyridine marine alkaloid analogue antimalarials and the heme group: an experimental and theoretical investigation
dc.typeArtigo de periódico
local.citation.epage579
local.citation.issue3
local.citation.spage571
local.citation.volume56
local.description.resumoSynthetic 3-alkylpyridine marine alkaloid (3-APA) analogues have shown good antimalarial activity against Plasmodium falciparum. However, despite their structural originality, their molecular target was unknown. Herein, we report a proposal for the antimalarial mechanism of action of 3-APA analogues through interference with the process of hemozoin (Hz) formation. The interaction between 3-APA analogues and heme groups was investigated employing an in silico approach and biophysical techniques such as ultraviolet–visible light (UV-vis) titration and electrospray ionization–mass spectrometry (ESI-MS). The in silico approach was performed based on pure ab initio electronic structure methods in order to obtain insights at the molecular level concerning the binding process of antimalarial drugs at their target site, the heme group. In silico results showed that the formation of heme:3-APA complexes at a molecular ratio of 2:1 are more stable than 1:1 complexes. These results were further confirmed by experimental techniques, such as UV-vis and high-resolution mass spectrometry (ESI-TOF), for two of the most active 3-APA analogues.
local.identifier.orcidhttps://orcid.org/0000-0001-6603-4770
local.identifier.orcidhttps://orcid.org/0000-0002-8073-3970
local.identifier.orcidhttps://orcid.org/0000-0002-6583-7958
local.identifier.orcidhttps://orcid.org/0000-0003-0546-2549
local.identifier.orcidhttps://orcid.org/0000-0001-6974-3724
local.identifier.orcidhttps://orcid.org/0000-0002-6341-1718
local.identifier.orcidhttps://orcid.org/0000-0002-2939-7780
local.identifier.orcidhttps://orcid.org/0000-0002-1521-7486
local.identifier.orcidhttps://orcid.org/0000-0002-2444-2554
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://pubs.acs.org/doi/10.1021/acs.jcim.5b00742

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