Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/107452
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Bártolo, Inês | - |
dc.contributor.author | Santos, Bruna S | - |
dc.contributor.author | Fontinha, Diana | - |
dc.contributor.author | Machado, Marta | - |
dc.contributor.author | Francisco, Denise | - |
dc.contributor.author | Sepodes, Bruno | - |
dc.contributor.author | Rocha, João | - |
dc.contributor.author | Mota-Filipe, Hélder | - |
dc.contributor.author | Pinto, Rui | - |
dc.contributor.author | Figueira, Maria E. | - |
dc.contributor.author | Barroso, Helena | - |
dc.contributor.author | Nascimento, Teresa | - |
dc.contributor.author | Alves de Matos, António P. | - |
dc.contributor.author | Alves, Américo J. S. | - |
dc.contributor.author | Alves, Nuno G. | - |
dc.contributor.author | Simões, Carlos J. V. | - |
dc.contributor.author | Prudêncio, Miguel | - |
dc.contributor.author | Pinho e Melo, Teresa M. V. D. | - |
dc.contributor.author | Taveira, Nuno | - |
dc.date.accessioned | 2023-07-12T11:55:03Z | - |
dc.date.available | 2023-07-12T11:55:03Z | - |
dc.date.issued | 2021-02-12 | - |
dc.identifier.issn | 2373-8227 | pt |
dc.identifier.issn | 2373-8227 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/107452 | - |
dc.description.abstract | The high burden of malaria and HIV/AIDS prevents economic and social progress in developing countries. A continuing need exists for development of novel drugs and treatment regimens for both diseases in order to address the tolerability and long-term safety concerns associated with current treatment options and the emergence of drug resistance. We describe new spiro-β-lactam derivatives with potent (nM) activity against HIV and Plasmodium and no activity against bacteria and yeast. The best performing molecule of the series, BSS-730A, inhibited both HIV-1 and HIV-2 replication with an IC50 of 13 ± 9.59 nM and P. berghei hepatic infection with an IC50 of 0.55 ± 0.14 μM with a clear impact on parasite development. BSS-730A was also active against the erythrocytic stages of P. falciparum, with an estimated IC50 of 0.43 ± 0.04 μM. Time-of-addition studies showed that BSS-730A potentially affects all stages of the HIV replicative cycle, suggesting a complex mechanism of action. BSS-730A was active against multidrug-resistant HIV isolates, with a median 2.4-fold higher IC50 relative to control isolates. BSS-730A was equally active against R5 and X4 HIV isolates and displayed strong synergism with the entry inhibitor AMD3100. BSS-730A is a promising candidate for development as a potential therapeutic and/or prophylactic agent against HIV and Plasmodium. | pt |
dc.language.iso | eng | pt |
dc.publisher | ACS American Chemical Society | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/UIDB/00313/2020 | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/UIDP/00313/2020 | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04138/2020/PT/Research Institute for Medicines | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP/04138/2020/PT/Research Institute for Medicines | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/SAU-INF/29550/2017/PT/Enabling strategies for enhanced whole-sporozoite malaria vaccines | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/OE/SFRH/BPD/76225/2011/PT/DESENVOLVIMENTO DE NOVOS MICROBICIDAS PARA PREVENIR A INFECÇÃO POR VIH | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/POR_CENTRO/PD/BD/135287/2017/PT/Broadening the spectrum of spito-B-lactams antiviral activity: from new targets identification to the discovery of new compounds with anti-influenza activity. | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/OE/SFRH/BD/128910/2017/PT/Novel spiro-lactams as new antimicrobial agents | pt |
dc.rights | embargoedAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | pt |
dc.subject | AIDS | pt |
dc.subject | BSS-730A | pt |
dc.subject | anti-HIV activity | pt |
dc.subject | antiplasmodial activity | pt |
dc.subject | malaria | pt |
dc.subject | spiro-β-lactams | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Plasmodium falciparum | pt |
dc.subject.mesh | beta-Lactams | pt |
dc.subject.mesh | Antimalarials | pt |
dc.subject.mesh | HIV Infections | pt |
dc.subject.mesh | Plasmodium | pt |
dc.title | Spiro-β-lactam BSS-730A Displays Potent Activity against HIV and Plasmodium | pt |
dc.type | article | - |
degois.publication.firstPage | 421 | pt |
degois.publication.lastPage | 434 | pt |
degois.publication.issue | 2 | pt |
degois.publication.title | Infectious Diseases | pt |
dc.relation.publisherversion | https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00768 | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1021/acsinfecdis.0c00768 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2022-02-12 | * |
uc.date.periodoEmbargo | 365 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CIEC – Interuniversitary Centre for Camonian Studies | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0003-3426-2490 | - |
crisitem.author.orcid | 0000-0001-5994-9104 | - |
crisitem.author.orcid | 0000-0003-3256-4954 | - |
Appears in Collections: | I&D CQC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Bartolo2021ACSInfectDis.pdf | 1.86 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
13
checked on May 6, 2024
WEB OF SCIENCETM
Citations
11
checked on May 2, 2024
Page view(s)
82
checked on May 7, 2024
Download(s)
54
checked on May 7, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License