Publicação
Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum
| Resumo: | We 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. |
|---|---|
| Autores principais: | Santos Barbosa, Patricia |
| Outros Autores: | Souza, Guilherme Eduardo; Maluf, Sarah El Chamy; Bonatto, Vinícius; Moura, Caio Silva; Mendes, Giovana Rossi; Valdes, Talita Alvarenga; Annunciato, Yasmin; Rossetto, Barbara dos Santos; Ventura, Priscilla Dantas de Souza; Ortin, Gilberto Gaspar Duarte; da Silva, Wellington; Icimoto, Marcelo Yudi; Ferreira, Amália dos Santos; Cruz, Fabio C.; Teles, Carolina B. G.; Pereira, Dhelio B.; Cassiano, Gustavo Capatti; Santana, Sofia; Prudêncio, Miguel; Barbosa, Camila S.; Moura, Igor M. R.; Giampauli, Renan Marcel; De Sousa, Irene Layane; Rocco, Silvana Aparecida; Gazarini, Marcos L.; Correia, Carlos Roque Duarte; Aguiar, Anna Caroline Campos; Guido, Rafael Victorio Carvalho |
| Assunto: | Molecular Medicine Drug Discovery |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868984234333437952 |
|---|---|
| author | Santos Barbosa, Patricia |
| author2 | Souza, Guilherme Eduardo Maluf, Sarah El Chamy Bonatto, Vinícius Moura, Caio Silva Mendes, Giovana Rossi Valdes, Talita Alvarenga Annunciato, Yasmin Rossetto, Barbara dos Santos Ventura, Priscilla Dantas de Souza Ortin, Gilberto Gaspar Duarte da Silva, Wellington Icimoto, Marcelo Yudi Ferreira, Amália dos Santos Cruz, Fabio C. Teles, Carolina B. G. Pereira, Dhelio B. Cassiano, Gustavo Capatti Santana, Sofia Prudêncio, Miguel Barbosa, Camila S. Moura, Igor M. R. Giampauli, Renan Marcel De Sousa, Irene Layane Rocco, Silvana Aparecida Gazarini, Marcos L. Correia, Carlos Roque Duarte Aguiar, Anna Caroline Campos Guido, Rafael Victorio Carvalho |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Santos Barbosa, Patricia Souza, Guilherme Eduardo Maluf, Sarah El Chamy Bonatto, Vinícius Moura, Caio Silva Mendes, Giovana Rossi Valdes, Talita Alvarenga Annunciato, Yasmin Rossetto, Barbara dos Santos Ventura, Priscilla Dantas de Souza Ortin, Gilberto Gaspar Duarte da Silva, Wellington Icimoto, Marcelo Yudi Ferreira, Amália dos Santos Cruz, Fabio C. Teles, Carolina B. G. Pereira, Dhelio B. Cassiano, Gustavo Capatti Santana, Sofia Prudêncio, Miguel Barbosa, Camila S. Moura, Igor M. R. Giampauli, Renan Marcel De Sousa, Irene Layane Rocco, Silvana Aparecida Gazarini, Marcos L. Correia, Carlos Roque Duarte Aguiar, Anna Caroline Campos Guido, Rafael Victorio Carvalho |
| author_role | author |
| contributor_name_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) ACS - American Chemical Society RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Santos Barbosa, Patricia\"},{\"Person.name\":\"Souza, Guilherme Eduardo\"},{\"Person.name\":\"Maluf, Sarah El Chamy\"},{\"Person.name\":\"Bonatto, Vinícius\"},{\"Person.name\":\"Moura, Caio Silva\"},{\"Person.name\":\"Mendes, Giovana Rossi\"},{\"Person.name\":\"Valdes, Talita Alvarenga\"},{\"Person.name\":\"Annunciato, Yasmin\"},{\"Person.name\":\"Rossetto, Barbara dos Santos\"},{\"Person.name\":\"Ventura, Priscilla Dantas de Souza\"},{\"Person.name\":\"Ortin, Gilberto Gaspar Duarte\"},{\"Person.name\":\"da Silva, Wellington\"},{\"Person.name\":\"Icimoto, Marcelo Yudi\"},{\"Person.name\":\"Ferreira, Amália dos Santos\"},{\"Person.name\":\"Cruz, Fabio C.\"},{\"Person.name\":\"Teles, Carolina B. G.\"},{\"Person.name\":\"Pereira, Dhelio B.\"},{\"Person.name\":\"Cassiano, Gustavo Capatti\"},{\"Person.name\":\"Santana, Sofia\"},{\"Person.name\":\"Prudêncio, Miguel\"},{\"Person.name\":\"Barbosa, Camila S.\"},{\"Person.name\":\"Moura, Igor M. R.\"},{\"Person.name\":\"Giampauli, Renan Marcel\"},{\"Person.name\":\"De Sousa, Irene Layane\"},{\"Person.name\":\"Rocco, Silvana Aparecida\"},{\"Person.name\":\"Gazarini, Marcos L.\"},{\"Person.name\":\"Correia, Carlos Roque Duarte\"},{\"Person.name\":\"Aguiar, Anna Caroline Campos\"},{\"Person.name\":\"Guido, Rafael Victorio Carvalho\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) ACS - American Chemical Society RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Santos Barbosa, Patricia Souza, Guilherme Eduardo Maluf, Sarah El Chamy Bonatto, Vinícius Moura, Caio Silva Mendes, Giovana Rossi Valdes, Talita Alvarenga Annunciato, Yasmin Rossetto, Barbara dos Santos Ventura, Priscilla Dantas de Souza Ortin, Gilberto Gaspar Duarte da Silva, Wellington Icimoto, Marcelo Yudi Ferreira, Amália dos Santos Cruz, Fabio C. Teles, Carolina B. G. Pereira, Dhelio B. Cassiano, Gustavo Capatti Santana, Sofia Prudêncio, Miguel Barbosa, Camila S. Moura, Igor M. R. Giampauli, Renan Marcel De Sousa, Irene Layane Rocco, Silvana Aparecida Gazarini, Marcos L. Correia, Carlos Roque Duarte Aguiar, Anna Caroline Campos Guido, Rafael Victorio Carvalho |
| datacite.date.Accepted.fl_str_mv | 2025-10-23T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-03-11T15:29:02Z |
| datacite.date.embargoed.fl_str_mv | 2026-03-11T15:29:02Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Molecular Medicine Drug Discovery |
| datacite.titles.title.fl_str_mv | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum SAR Analysis, Mode of Action and In Vivo Studies |
| dc.contributor.none.fl_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) ACS - American Chemical Society RUN |
| dc.creator.none.fl_str_mv | Santos Barbosa, Patricia Souza, Guilherme Eduardo Maluf, Sarah El Chamy Bonatto, Vinícius Moura, Caio Silva Mendes, Giovana Rossi Valdes, Talita Alvarenga Annunciato, Yasmin Rossetto, Barbara dos Santos Ventura, Priscilla Dantas de Souza Ortin, Gilberto Gaspar Duarte da Silva, Wellington Icimoto, Marcelo Yudi Ferreira, Amália dos Santos Cruz, Fabio C. Teles, Carolina B. G. Pereira, Dhelio B. Cassiano, Gustavo Capatti Santana, Sofia Prudêncio, Miguel Barbosa, Camila S. Moura, Igor M. R. Giampauli, Renan Marcel De Sousa, Irene Layane Rocco, Silvana Aparecida Gazarini, Marcos L. Correia, Carlos Roque Duarte Aguiar, Anna Caroline Campos Guido, Rafael Victorio Carvalho |
| dc.date.Accepted.fl_str_mv | 2025-10-23T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-03-11T15:29:02Z |
| dc.date.embargoed.fl_str_mv | 2026-03-11T15:29:02Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/201282 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Molecular Medicine Drug Discovery |
| dc.title.fl_str_mv | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum SAR Analysis, Mode of Action and In Vivo Studies |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | We 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/5c2c73b3-23df-4bdf-9aad-93188073e1df/download |
| id | run_615d4cbff84e6f8407dc7ff3f2d8afaf |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/201282 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
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| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/201282 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Santos Barbosa, Patricia Souza, Guilherme Eduardo Maluf, Sarah El Chamy Bonatto, Vinícius Moura, Caio Silva Mendes, Giovana Rossi Valdes, Talita Alvarenga Annunciato, Yasmin Rossetto, Barbara dos Santos Ventura, Priscilla Dantas de Souza Ortin, Gilberto Gaspar Duarte da Silva, Wellington Icimoto, Marcelo Yudi Ferreira, Amália dos Santos Cruz, Fabio C. Teles, Carolina B. G. Pereira, Dhelio B. Cassiano, Gustavo Capatti Santana, Sofia Prudêncio, Miguel Barbosa, Camila S. Moura, Igor M. R. Giampauli, Renan Marcel De Sousa, Irene Layane Rocco, Silvana Aparecida Gazarini, Marcos L. Correia, Carlos Roque Duarte Aguiar, Anna Caroline Campos Guido, Rafael Victorio Carvalho |
| publishDate | 2025 |
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| reponame_str | Repositório Institucional da UNL |
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| spelling | engenWe 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.application/pdfenFluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparumSubtitleenSAR Analysis, Mode of Action and In Vivo StudiesSantos Barbosa, PatriciaSouza, Guilherme EduardoMaluf, Sarah El ChamyBonatto, ViníciusMoura, Caio SilvaMendes, Giovana RossiValdes, Talita AlvarengaAnnunciato, YasminRossetto, Barbara dos SantosVentura, Priscilla Dantas de SouzaOrtin, Gilberto Gaspar Duarteda Silva, WellingtonIcimoto, Marcelo YudiFerreira, Amália dos SantosCruz, Fabio C.Teles, Carolina B. G.Pereira, Dhelio B.Cassiano, Gustavo CapattiSantana, SofiaPrudêncio, MiguelBarbosa, Camila S.Moura, Igor M. R.Giampauli, Renan MarcelDe Sousa, Irene LayaneRocco, Silvana AparecidaGazarini, Marcos L.Correia, Carlos Roque DuarteAguiar, Anna Caroline CamposGuido, Rafael Victorio CarvalhoLaboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)Vector borne diseases and pathogens (VBD)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)ACS - American Chemical SocietyHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf0022-2623URNIsPartOfPURE: 152514430URNIsPartOfPURE UUID: d4cb10d7-e7ab-4737-a188-8183ea22561cURNIsPartOfScopus: 105019589475URNIsPartOfWOS: 001584713400001URNIsPartOfPubMed: 41026123URNIsPartOfPubMedCentral: PMC12557366DOIIsPartOf10.1021/acs.jmedchem.5c001382026-03-11T15:29:02Z2025-10-232025-10-23T00:00:00ZHandlehttp://hdl.handle.net/10362/201282http://purl.org/coar/access_right/c_abf2open accessMolecular MedicineDrug Discovery12828731 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/5c2c73b3-23df-4bdf-9aad-93188073e1df/download |
| spellingShingle | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum Santos Barbosa, Patricia Molecular Medicine Drug Discovery |
| status | SINGLETON |
| subject.fl_str_mv | Molecular Medicine Drug Discovery |
| title | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| title_full | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| title_fullStr | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| title_full_unstemmed | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| title_short | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| title_sort | Fluorescent Marinoquinoline Derivative as Inhibitors of Plasmodium falciparum |
| topic | Molecular Medicine Drug Discovery |
| topic_facet | Molecular Medicine Drug Discovery |
| url | http://hdl.handle.net/10362/201282 |
| visible | 1 |