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Unveiling a family of spiro-β-lactams with anti-HIV and antiplasmodial activity via phosphine-catalyzed [3+2] annulation of 6-alkylidene-penicillanates and allenoates

2022-10Contribution to journal Open access
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datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorAlves, Américo J. S.
dc.contributor.authorAlves, Nuno G.
dc.contributor.authorBártolo, Inês
dc.contributor.authorFontinha, Diana
dc.contributor.authorCaetano, Soraia
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorTaveira, Nuno
dc.contributor.authorMelo, Teresa M. V. D. Pinho e
dc.date.accessioned2025-12-02T16:46:52Z
dc.date.available2025-12-02T16:46:52Z
dc.date.issued2022-10
dc.description.abstractThe molecular architecture of spirocyclic compounds has been widely explored within the medicinal chemistry field to obtain new compounds with singular three-dimensional pharmacophoric features and improved bioactivity. Herein, the synthesis of 68 new spirocyclopentene-β-lactams is described, resulting from a rational drug design and structural modulation of a highly promising lead compound BSS-730A, previously identified as having dual antimicrobial activity associated with a novel mechanism of action. Among this diverse library of new compounds, 22 were identified as active against HIV-1, with eight displaying an IC50 lower than 50 nM. These eight compounds also showed nanomolar activity against HIV-2, and six of them displayed micromolar antiplasmodial activity against both the hepatic and the blood stages of infection by malaria parasites, in agreement with the lead molecule’s bioactivity profile. The spirocyclopentene-β-lactams screened also showed low cytotoxicity against TZM-bl and Huh7 human cell lines. Overall, a family of new spirocyclopentene penicillanates with potent activity against HIV and/or Plasmodium was identified. The present structure–activity relationship open avenues for further development of spirocyclopentene-β-lactams as multivalent, highly active broad spectrum antimicrobial agents.eng
dc.identifier.citationAlves AJS, Alves NG, Bártolo I, Fontinha D, Caetano S, Prudêncio M, Taveira N and Pinho e Melo TMVD (2022) Unveiling a family of spiro-β-lactams with anti-HIV and antiplasmodial activity via phosphine-catalyzed [3+2] annulation of 6-alkylidene-penicillanates and allenoates. Front. Chem. 10:1017250. doi: 10.3389/fchem.2022.1017250
dc.identifier.doi10.3389/fchem.2022.1017250
dc.identifier.issn2296-2646
dc.identifier.urihttp://hdl.handle.net/10400.26/60174
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media
dc.relation.hasversionhttps://doi.org/10.3389/fchem.2022.1017250
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectspiro-penicillanates
dc.subjectβ-Lactams
dc.subjectspirocyclic compounds
dc.subjectspiro-β-lactams
dc.subjectallenoates
dc.subjectanti-HIV
dc.subjectantiplasmodial activities
dc.subjectphosphane-catalyzed annulations
dc.titleUnveiling a family of spiro-β-lactams with anti-HIV and antiplasmodial activity via phosphine-catalyzed [3+2] annulation of 6-alkylidene-penicillanates and allenoateseng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.startPage1017250
oaire.citation.titleFrontiers in Chemistry
oaire.citation.volume10
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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