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Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes

2022-06-27Artigo científico Acesso aberto
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dc.contributor.authorLe Gal, Yann
dc.contributor.authorFilatre-Furcate, Agathe
dc.contributor.authorLorcy, Dominique
dc.contributor.authorJeannin, Olivier
dc.contributor.authorRoisnel, Thierry
dc.contributor.authorDorcet, Vincent
dc.contributor.authorFontinha, Diana
dc.contributor.authorFrancisco, Denise
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorMartins, Marta
dc.contributor.authorSoeiro, Catarina
dc.contributor.authorSousa, Sílvia A.
dc.contributor.authorLeitão, Jorge H.
dc.contributor.authorMorais, Tânia
dc.contributor.authorBártolo, Inês
dc.contributor.authorTaveira, Nuno
dc.contributor.authorGuerreiro, Joana F.
dc.contributor.authorMarques, Fernanda
dc.date.accessioned2023-08-21T18:08:23Z
dc.date.available2023-08-21T18:08:23Z
dc.date.issued2022-06-27
dc.date.updated2023-02-03T12:10:59Z
dc.description.abstractThe biological properties of sixteen structurally related monoanionic gold (III) bis(dithiolene/diselenolene) complexes were evaluated. The complexes differ in the nature of the heteroatom connected to the gold atom (AuS for dithiolene, AuSe for diselenolene), the substituent on the nitrogen atom of the thiazoline ring (Me, Et, Pr, iPr and Bu), the nature of the exocyclic atom or group of atoms (O, S, Se, C(CN)2) and the counter-ion (Ph4P+ or Et4N+). The anticancer and antimicrobial activities of all the complexes were investigated, while the anti-HIV activity was evaluated only for selected complexes. Most complexes showed relevant anticancer activities against Cisplatin-sensitive and Cisplatin-resistant ovarian cancer cells A2780 and OVCAR8, respectively. After 48 h of incubation, the IC50 values ranged from 0.1–8 µM (A2780) and 0.8–29 µM (OVCAR8). The complexes with the Ph4P+ ([P]) counter-ion are in general more active than their Et4N+ ([N]) analogues, presenting IC50 values in the same order of magnitude or even lower than Auranofin. Studies in the zebrafish embryo model further showed that, despite their marked anticancer effect, the complexes with [P] counter-ion exhibited low in vivo toxicity. In general, the exocyclic exchange of sulfur by oxygen or ylidenemalononitrile (C(CN)2) enhanced the compounds toxicity. Most complexes containing the [P] counter ion exhibited exceptional antiplasmodial activity against the Plasmodium berghei parasite liver stages, with submicromolar IC50 values ranging from 400–700 nM. In contrast, antibacterial/fungi activities were highest for most complexes with the [N] counter-ion. Auranofin and two selected complexes [P][AuSBu(=S)] and [P][AuSEt(=S)] did not present anti-HIV activity in TZM-bl cells. Mechanistic studies for selected complexes support the idea that thioredoxin reductase, but not DNA, is a possible target for some of these complexes. The complexes [P] [AuSBu(=S)], [P] [AuSEt(=S)], [P] [AuSEt(=Se)] and [P] [AuSeiPr(=S)] displayed a strong quenching of the fluorescence intensity of human serum albumin (HSA), which indicates a strong interaction with this protein. Overall, the results highlight the promising biological activities of these complexes, warranting their further evaluation as future drug candidates with clinical applicability.pt_PT
dc.description.sponsorshipThe Portuguese team thank the Fundação para a Ciência e Tecnologia (FCT) for the financial support through the projects UID/MULTI/04349/2019 (C2TN), UIDB/00100/2020 (CQE), UIDB/04565/2020 and UIDP/04565/2020 (iBB) and LA/P/0140/2020 (Associate Laboratory Institute for Health and Bioeconomy—i4HB. T.S. Morais thanks FCT for CEECIND 2017 Initiative for the project CEECIND/00630/2017 (acknowledging FCT, POPH and ESF—European Social Fund).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLe Gal Y, Filatre-Furcate A, Lorcy D, Jeannin O, Roisnel T, Dorcet V, et al. Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes. International Journal of Molecular Sciences [Internet]. 2022 Jun 27;23(13):7146. Available from: http://dx.doi.org/10.3390/ijms23137146pt_PT
dc.identifier.doi10.3390/ijms23137146pt_PT
dc.identifier.issn1422-0067
dc.identifier.slugcv-prod-3091875
dc.identifier.urihttp://hdl.handle.net/10451/58947
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationLA/P/0140/2020pt_PT
dc.relationCentre for Nuclear Sciences and Technologies
dc.relationCentro de Química Estrutural
dc.relationInstitute for Bioengineering and Biosciences
dc.relationInstitute for Bioengineering and Biosciences
dc.relationNot Available
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/23/13/7146pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectgold bis(dithiolene) complexespt_PT
dc.subjectdiselenolenept_PT
dc.subjectstructural modificationpt_PT
dc.subjectanticancer activitypt_PT
dc.subjectantimicrobial activitypt_PT
dc.subjectHSA interactionpt_PT
dc.titleBroad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexespt_PT
dc.typejournal article
dspace.entity.typePublication
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oaire.awardTitleCentre for Nuclear Sciences and Technologies
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oaire.citation.issue13pt_PT
oaire.citation.startPage7146pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
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