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Spiro-Lactams as Novel Antimicrobial Agents

2020-02-19Artigo científico Desconhecido
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dc.contributor.authorAlves, Américo
dc.contributor.authorG. Alves, Nuno
dc.contributor.authorCaratão, Cátia
dc.contributor.authorEsteves, Margarida
dc.contributor.authorFontinha, Diana
dc.contributor.authorBártolo, Inês
dc.contributor.authorSoares, Maria I. L.
dc.contributor.authorLopes, Susana M. M.
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorTaveira, Nuno
dc.contributor.authorMelo, Teresa M. V. D. Pinho E
dc.date.accessioned2023-08-22T16:57:33Z
dc.date.available2023-08-22T16:57:33Z
dc.date.issued2020-02-19
dc.date.updated2023-02-03T12:38:29Z
dc.description.abstractIntroduction: Structural modulation of previously identified lead spiro-β-lactams with antimicrobial activity was carried out. Objective: The main objective of this work was to synthesize and evaluate the biological activity of novel spiro-lactams based on previously identified lead compounds with antimicrobial activity. Methods: The target chiral spiro-γ-lactams were synthesized through 1,3-dipolar cycloaddition reaction of a diazo-γ-lactam with electron-deficient dipolarophiles. In vitro activity against HIV and Plasmodium of a wide range of spiro-β-lactams and spiro-γ-lactams was evaluated. Among these compounds, one derivative with good anti-HIV activity and two with promising antiplasmodial activity (IC50 < 3.5 µM) were identified. Results: A novel synthetic route to chiral spiro-γ-lactams has been established. The studied β- and γ- lactams were not cytotoxic, and three compounds with promising antimicrobial activity were identified, whose structural modulation may lead to new and more potent drugs. Conclusion: The designed structural modulation of biologically active spiro-β-lactams involved the replacement of the four-membered β-lactam ring by a five-membered γ-lactam ring. Although conformational and superimposition computational studies revealed no significant differences between β- and γ- lactam pharmacophoric features, the studied structural modulation did not lead to compounds with a similar biological profile. The observed results suggest that the β-lactamic core is a requirement for the activity against both HIV and Plasmodium.pt_PT
dc.description.sponsorshipAmérico J. S. Alves, Nuno G. Alves, Cátia C. Caratão, Margarida I. M. Esteves, Maria I. L. Soares, Susana M. M. Lopes and Teresa M. V. D. Pinho e Melo, thank to the Coimbra Chemistry Centre (CQC) supported by the Portuguese Agency for Scientific Research, “Fundação para a Ciência e a Tecnologia” (FCT), through Project UID/QUI/00313/2019. Américo J. S. Alves and Nuno G. Alves thank FCT for fellowships SFRH/BD/128910/2017 and PD/BD/135287/2017, respectively. Miguel Prudêncio acknowledges FCT for grant PTDC-SAU-INF-29550-2017 and contract CEEC-2017.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlves AJS, Alves NG, Caratão CC, Esteves MIM, Fontinha D, Bártolo I, et al. Spiro-lactams as novel antimicrobial agents. Current Topics in Medicinal Chemistry [Internet]. 2020;20(2):140–52. Disponível em: https://www.eurekaselect.com/article/102088pt_PT
dc.identifier.doi10.2174/1568026619666191105110049pt_PT
dc.identifier.eid2-s2.0-85080850781
dc.identifier.slugcv-prod-1108443
dc.identifier.urihttp://hdl.handle.net/10451/58962
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBentham Sciencept_PT
dc.relationPTDC-SAU-INF-29550-2017pt_PT
dc.relationCoimbra Chemistry Center
dc.relationNovel spiro-lactams as new antimicrobial agents
dc.relationBroadening the spectrum of spito-B-lactams antiviral activity: from new targets identification to the discovery of new compounds with anti-influenza activity.
dc.relation.publisherversionhttps://www.eurekaselect.com/article/102088pt_PT
dc.subjectAnti-HIV Agentspt_PT
dc.subjectAntiplasmodial Agentspt_PT
dc.subjectSpiro-γ-lactamspt_PT
dc.subjectSpiro-penicillanatept_PT
dc.subject5-Oxohexahydropyrrolo[2, 1- b]thiazolespt_PT
dc.subjectDipolar Cycloadditionpt_PT
dc.subjectDiazo Compoundspt_PT
dc.titleSpiro-Lactams as Novel Antimicrobial Agentspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberUID/QUI/00313/2019
oaire.awardNumberSFRH/BD/128910/2017
oaire.awardNumberPD/BD/135287/2017
oaire.awardTitleCoimbra Chemistry Center
oaire.awardTitleNovel spiro-lactams as new antimicrobial agents
oaire.awardTitleBroadening the spectrum of spito-B-lactams antiviral activity: from new targets identification to the discovery of new compounds with anti-influenza activity.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00313%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F128910%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F135287%2F2017/PT
oaire.citation.endPage152pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage140pt_PT
oaire.citation.titleCurrent Topics in Medicinal Chemistrypt_PT
oaire.citation.volume20pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
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