Selagibenzophenone B and Its Derivatives: SelB-1, a Dual Topoisomerase I/II Inhibitor Identified through In Vitro and In Silico Analyses

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dc.authoridLapinskaite, Ringaile/0000-0002-7865-9660
dc.authoridDonmez, Serhat/0000-0002-6301-7243
dc.authoridRycek, Lukas/0000-0003-3028-8829
dc.authoridAtalay, Hazal Nazlican/0000-0001-8859-0268
dc.contributor.authorDonmez, Serhat
dc.contributor.authorLapinskaite, Ringaile
dc.contributor.authorAtalay, Hazal Nazlican
dc.contributor.authorTokay, Esra
dc.contributor.authorKockar, Feray
dc.contributor.authorRycek, Lukas
dc.contributor.authorOzbil, Mehmet
dc.date.accessioned2025-01-27T20:43:34Z
dc.date.available2025-01-27T20:43:34Z
dc.date.issued2024
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractThe development of multitargeted drugs represents an innovative approach to cancer treatment, aiming to enhance drug effectiveness while minimizing side effects. Herein, we sought to elucidate the inhibitory effect of selagibenzophenone B derivatives on the survival of cancer cells and dual topoisomerase I/II enzyme activity. Results demonstrated that among the compounds, SelB-1 selectively inhibited the proliferation and migration of prostate cancer cells while exhibiting minimal effects on healthy cells. Furthermore, SelB-1 showed a dual inhibitory effect on topoisomerases. Computational analyses mirrored the results from enzyme inhibition assays, demonstrating the compound's strong binding affinity to the catalytic sites of the topoisomerases. To our surprise, SelB-1 did not induce apoptosis in prostate cancer cells; instead, it induced autophagic gene expression and lipid peroxidation while reducing GSH levels, which might be associated with ferroptotic death mechanisms. To summarize, the findings suggest that SelB-1 possesses the potential to serve as a dual topoisomerase inhibitor and can be further developed as a promising candidate for prostate cancer treatment.
dc.description.sponsorshipCanakkale Onsekiz Mart University [FIA-2021-3666, FYL-2022-4122]
dc.description.sponsorshipThis research was funded by the Canakkale Onsekiz Mart University (Scientific Research Projects), grant numbers FIA-2021-3666 and FYL-2022-4122. The molecular dynamics simulations reported in this paper were performed at the TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).
dc.identifier.doi10.1021/acsbiomedchemau.4c00027
dc.identifier.endpage189
dc.identifier.issn2694-2437
dc.identifier.issue4
dc.identifier.pmid39184056
dc.identifier.scopus2-s2.0-85199708123
dc.identifier.scopusqualityQ2
dc.identifier.startpage178
dc.identifier.urihttps://doi.org/10.1021/acsbiomedchemau.4c00027
dc.identifier.urihttps://hdl.handle.net/20.500.12428/24271
dc.identifier.volume4
dc.identifier.wosWOS:001279686700001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofAcs Bio & Med Chem Au
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectcancer
dc.subjectdual inhibition
dc.subjectin silico moleculardocking
dc.subjectin vitro
dc.subjecttopoisomerase
dc.titleSelagibenzophenone B and Its Derivatives: SelB-1, a Dual Topoisomerase I/II Inhibitor Identified through In Vitro and In Silico Analyses
dc.typeArticle

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