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Insight into the reactivity and antitumoral potential of allyl rhodanine derivatives

2026-09-15Artigo científico Acesso aberto
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dc.contributor.authorEr-raqioui, Redouane
dc.contributor.authorCavaleiro, José A. S.
dc.contributor.authorFaustino, M. Amparo F.
dc.contributor.authorPaz, Filipe A .Almeida
dc.contributor.authorViale, Maurizio
dc.contributor.authorLoiacono, Fabrizio
dc.contributor.authorRakib, El Mostapha
dc.contributor.authorNeves, Maria da Graça P. M. S.
dc.contributor.authorPereira, Florbela
dc.contributor.authorMoura, Nuno M. M.
dc.contributor.institutionLAQV@REQUIMTE
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblElsevier Science B.V., Amsterdam.
dc.date.accessioned2026-07-24T14:43:01Z
dc.date.available2026-07-24T14:43:01Z
dc.date.issued2026-09-15
dc.descriptionPublisher Copyright: © 2026 The Authors.
dc.description.abstractIn this work, a series of N -allyl-5-arylidene-rhodanine derivatives was prepared and their reactivity evaluated as dipolarophiles in 1,3-dipolar cycloaddition reactions. Cycloadducts of series 5 were obtained using sarcosine and 5-nitroisatin as precursors, while reactions with sarcosine and 2-pyridinecarboxaldehyde afforded new 2-pyridyl-substituted spiro derivatives (series 7). All compounds from both series were fully characterized and screened for their in vitro anticancer activity against the following five human cancer cell lines: A2780 (ovarian carcinoma), A549 (lung adenocarcinoma), MDA-MB-231 (breast carcinoma), NCI-N592 (small-cell lung cancer), and A431 (epidermoid carcinoma). Several derivatives exhibited pharmacologically relevant IC50 values, with compounds 5b and 7b demonstrating noteworthy antiproliferative activity in A549 cells, a standard model for non-small cell lung carcinoma. The apoptotic potential of the most active compounds was further confirmed by Annexin V/PI assays in A549 cells. Using baicalein as a reference inhibitor, both compound series were also subjected to molecular docking studies targeting the human enzyme 15-lipoxygenase-2 (h15-LOX-2), implicated in cancer-related pathways. In general, a consistent trend was observed between the antiproliferative activity of the compounds and their predicted inhibition of h 15-LOX-2, as inferred from docking analysis of 28 structures, including the 10 final allyl rhodanine-based compounds and their required precursors. To further evaluate target engagement, molecular dynamics (MD) simulations were performed for the most active derivatives, providing mechanistic insight into binding-pocket rigidification and conformational stability. In addition, in silico ADMET predictions were carried out to assess the developability profile of the lead candidates. The integrated chemical synthesis, biological evaluation, and computational modeling provided key insights into the reactivity, bioactivity, and structure–activity relationships of the synthesized compounds.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent13
dc.format.extent3235139
dc.identifier.doi10.1016/j.bioorg.2026.110154
dc.identifier.issn0045-2068
dc.identifier.otherPURE: 169315611
dc.identifier.otherPURE UUID: bfa476e1-73d5-4d4a-b662-f49c743afc1a
dc.identifier.otherScopus: 105042741094
dc.identifier.otherWOS: 001812254900001
dc.identifier.otherPubMed: 42364378
dc.identifier.otherORCID: /0000-0003-4392-4644/work/221755537
dc.identifier.urihttp://hdl.handle.net/10362/204833
dc.identifier.urlhttps://www.scopus.com/pages/publications/105042741094
dc.identifier.urlhttps://www.webofscience.com/wos/woscc/full-record/WOS:001812254900001
dc.language.isoeng
dc.peerreviewedyes
dc.subjectADMET
dc.subjectAntitumoral
dc.subjectMolecular docking
dc.subjectMolecular dynamics
dc.subjectRhodanine
dc.subjectSpiro compounds
dc.subject[3 + 2] cycloaddition
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectDrug Discovery
dc.subjectOrganic Chemistry
dc.subjectSDG 3 - Good Health and Well-being
dc.titleInsight into the reactivity and antitumoral potential of allyl rhodanine derivativesen
dc.title.subtitleAzomethine ylide cycloadditions, molecular docking, and SAR studiesen
dc.typejournal article
degois.publication.firstPage1
degois.publication.lastPage13
degois.publication.titleBioorganic Chemistry
degois.publication.volume180
dspace.entity.typePublication
rcaap.rightsopenAccess

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