Design, synthesis, characterization, computational analysis, structure-activity relationship, and investigation of the anticancer potential of novel dibromodibenzoazepine-based hybrid structures

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dc.authorid0000-0002-4037-1979
dc.contributor.authorAllito, Azza
dc.contributor.authorOnder, Alper
dc.contributor.authorOnder, Ferah Comert
dc.contributor.authorErdogan, Musa
dc.date.accessioned2026-02-03T12:03:00Z
dc.date.available2026-02-03T12:03:00Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractIn this study, ten novel dibromodibenzoazepine-substituted triazole hybrid compounds (AZ1-AZ10) were designed via a molecular hybridization approach and synthesized using click chemistry methodology. In the synthesis, the dibromodibenzoazepine derivative (12) was initially synthesized via bromination. Subsequent propargylation yielded the key intermediate, dibromodibenzoazepine-propargyl derivative (13). The Cu (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of propargyl derivative (13) with various substituted azide derivatives afforded the target hybrid compounds in high yields. The structures of these compounds were characterized using various spectroscopic techniques, including H-1 NMR, C-13 NMR, and MS. Among the synthesized compounds, AZ9 was determined to have the highest cytotoxicity on breast and colon cancer cell lines, including BT20, MCF7, MDA-MB-231, and HT29 with the IC50 values of 0.54 +/- 0.09 mu M, 1.83 +/- 0.87 mu M, 3.88 +/- 0.15 mu M, and 5.31 +/- 0.38 mu M, respectively. In addition, AZ8 showed the cytotoxicity on BT20 and HT29 cells below 10 mu M. The cytotoxicity of AZ10 in studied cancer cell lines was calculated below 20 mu M. The compounds were investigated by computational analysis including molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA), and ADME predictions. As a result, AZ8-AZ10 may be promising anticancer agents targeting SphK1 and CDK6 to provide new perspectives for the design and development of novel click products.
dc.description.sponsorshipThe authors are grateful to Prof. Dr. Zuhal Hamurcu (Erciyes University) and Prof. Dr. Tu & gbreve;ba Tumer (Canakkale Onsekiz Mart University) for providing breast and colon cancer cell lines. This research has been supported by the Kafkas University Scientific Research Projects Coordination Unit (Project Number: 2023-FM-105). The authors are grateful to the Research Foundation of Kafkas University for financial support under project 2023-FM-105.
dc.identifier.doi10.1007/s11030-025-11418-w
dc.identifier.issn1381-1991
dc.identifier.issn1573-501X
dc.identifier.pmid41335181
dc.identifier.scopus2-s2.0-105023984597
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1007/s11030-025-11418-w
dc.identifier.urihttps://hdl.handle.net/20.500.12428/34932
dc.identifier.wosWOS:001634191000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Diversity
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260130
dc.subjectDibenzoazepine
dc.subjectTriazole
dc.subjectClick chemistry
dc.subjectAnticancer
dc.subjectMD simulation
dc.titleDesign, synthesis, characterization, computational analysis, structure-activity relationship, and investigation of the anticancer potential of novel dibromodibenzoazepine-based hybrid structures
dc.typeArticle

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