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Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum

2025-10-23Artigo científico Acesso aberto
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dc.contributor.authorSantos Barbosa, Patricia
dc.contributor.authorSouza, Guilherme Eduardo
dc.contributor.authorMaluf, Sarah El Chamy
dc.contributor.authorBonatto, Vinícius
dc.contributor.authorMoura, Caio Silva
dc.contributor.authorMendes, Giovana Rossi
dc.contributor.authorValdes, Talita Alvarenga
dc.contributor.authorAnnunciato, Yasmin
dc.contributor.authorRossetto, Barbara dos Santos
dc.contributor.authorVentura, Priscilla Dantas de Souza
dc.contributor.authorOrtin, Gilberto Gaspar Duarte
dc.contributor.authorda Silva, Wellington
dc.contributor.authorIcimoto, Marcelo Yudi
dc.contributor.authorFerreira, Amália dos Santos
dc.contributor.authorCruz, Fabio C.
dc.contributor.authorTeles, Carolina B. G.
dc.contributor.authorPereira, Dhelio B.
dc.contributor.authorCassiano, Gustavo Capatti
dc.contributor.authorSantana, Sofia
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorBarbosa, Camila S.
dc.contributor.authorMoura, Igor M. R.
dc.contributor.authorGiampauli, Renan Marcel
dc.contributor.authorDe Sousa, Irene Layane
dc.contributor.authorRocco, Silvana Aparecida
dc.contributor.authorGazarini, Marcos L.
dc.contributor.authorCorreia, Carlos Roque Duarte
dc.contributor.authorAguiar, Anna Caroline Campos
dc.contributor.authorGuido, Rafael Victorio Carvalho
dc.contributor.institutionLaboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)
dc.contributor.institutionVector borne diseases and pathogens (VBD)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblACS - American Chemical Society
dc.date.accessioned2026-03-11T15:29:02Z
dc.date.available2026-03-11T15:29:02Z
dc.date.issued2025-10-23
dc.descriptionFunding information: We acknowledge financial support from the São Paulo Research Foundation (FAPESP grants 2014/25770-6, 2013/07600-3, and 2023/00383-9 to C.R.D.C.; 2018/03143-0 to P.S.B., 2018/07287-7 to G.E.S.; 2023/09209-1 to V.B.; 2020/14429-2 to S.E.C.M.; 2022/01063-5 to G.R.M.; 2024/04949-0 to T.A.V.; 2022/03731-5, and 2023/03295-3 to W.S.; 2021/03977-1 to I.M.R.M.; 2013/07600-3, 2020/12904-5, and 2024/04805-8 to R.V.C.G.; 2019/19708-0 to A.C.C.A.), the Brazilian National Research Council (CNPq grants 457027/2014-2, and 305387/2013-8 to C.R.D.C.; 133404/2018-8 to G.G.D.O.; 142488/2020-8 to W.S.; 310602/2021-1 and 303062/2025-8 to R.V.C.G.), and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior─Brasil (CAPES)─Finance Code 001. We acknowledge Dr. Daniela Trivella, and Dr. Marjorie Bruder, from LNBio/CNPEM, for HRMS analyses during the pandemic of COVID-19 as well as the doctoral student Christian Herrera for the support with the chemistry. The authors also acknowledge Selvita S.A. (Kraków, Poland) for making the predictions. M.P. acknowledges the “la Caixa” Foundation (Spain)’s grant HR21-848 and European Union Horizon Europe programme grant 101080744 for support. We also thank the computational resources provided by “Centro Nacional de Processamento de Alto Desempenho em São Paulo (CENAPAD-SP)”. Publisher Copyright: © 2025 The Authors. Published by American Chemical Society
dc.description.abstractWe present insights into the mechanism of action of marinoquinolines (MQ), a novel class of lead candidates. Using a divergent synthetic approach, we developed a series of 20 new analogues with fluorescence properties. Structure–activity relationships analysis identified 19 as an attractive compound showing a combination of favorable in vitro (IC503D7= 0.28 μM; CC50HepG2= 53 μM), ex vivo (EC50Pf= 1.2 μM; EC50Pv= 0.53 μM), in vivo (3 × 50 mg/kg oral dose resulted in a 96% reduction in parasitemia in Plasmodium berghei-infected mice), physicochemical (Sol7.4= 171 μM; LogD7.4= 3.9), and pharmacokinetic (P_app = 9.4 × 10–6cm/s, human Clinthep,mic= 0.61–0.68 μL min–1mg–1) properties. Compound 19 selectively accumulates in infected erythrocytes, enters the digest vacuole and inhibits Plasmodium falciparum proteolytic activity, suggesting that MQs act as protease inhibitors. These findings strengthen the evidence that MQs are promising lead candidates for antimalarial drug discovery.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent24
dc.format.extent12828731
dc.identifier.doi10.1021/acs.jmedchem.5c00138
dc.identifier.issn0022-2623
dc.identifier.otherPURE: 152514430
dc.identifier.otherPURE UUID: d4cb10d7-e7ab-4737-a188-8183ea22561c
dc.identifier.otherScopus: 105019589475
dc.identifier.otherWOS: 001584713400001
dc.identifier.otherPubMed: 41026123
dc.identifier.otherPubMedCentral: PMC12557366
dc.identifier.urihttp://hdl.handle.net/10362/201282
dc.identifier.urlhttps://www.scopus.com/pages/publications/105019589475
dc.language.isoeng
dc.peerreviewedyes
dc.subjectMolecular Medicine
dc.subjectDrug Discovery
dc.titleFluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparumen
dc.title.subtitleSAR Analysis, Mode of Action and In Vivo Studiesen
dc.typejournal article
degois.publication.firstPage21120
degois.publication.issue20
degois.publication.lastPage21143
degois.publication.titleJournal Of Medicinal Chemistry
degois.publication.volume68
dspace.entity.typePublication
rcaap.rightsopenAccess

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