Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II?

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dc.contributor.authorKaratas, Esin
dc.contributor.authorFoto, Egemen
dc.contributor.authorErtan-Bolelli, Tugba
dc.contributor.authorYalcin-Ozkat, Gozde
dc.contributor.authorYilmaz, Serap
dc.contributor.authorAtaei, Sanaz
dc.contributor.authorZilifdar, Fatma
dc.date.accessioned2024-02-23T14:02:14Z
dc.date.available2024-02-23T14:02:14Z
dc.date.issued2021
dc.departmentNEÜen_US
dc.description.abstractDiscovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I and hTopo II alpha). Biological activity results were found very promising for the future due to two compounds, 5-nitro-2-(4butylphenyl)benzoxazole (1i) and 2-(4-butylphenyl)oxazolo[4,5-b]pyridine (2i), that inhibited hTopo II alpha with 2 mu M IC50 value. These two compounds were also found to be more active than reference drug etoposide. However, 1i and 2i did not show any satisfactory cyctotoxic activity on the HeLa, WiDR, A549, and MCF7 cancer cell lines. Moreover, molecular docking and molecular dynamic simulations studies for the most active compounds were applied in order to understand the mechanism of inhibition activity of hTopo II alpha. In addition, in silico ADME/Tox studies were performed to predict drug-likeness and pharmacokinetic properties of all the tested compounds.en_US
dc.identifier.doi10.1016/j.bioorg.2021.104913
dc.identifier.issn0045-2068
dc.identifier.issn1090-2120
dc.identifier.pmid33945950en_US
dc.identifier.scopus2-s2.0-85104975653en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2021.104913
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11638
dc.identifier.volume112en_US
dc.identifier.wosWOS:000661873800011en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAcademic Press Inc Elsevier Scienceen_US
dc.relation.ispartofBioorganic Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBenzoxazolesen_US
dc.subjectOxazolo[4,5-B]Pyridinesen_US
dc.subjectTopoisomerase I And Ii Alpha Inhibitionen_US
dc.subjectAntitumoren_US
dc.subjectMolecular Dockingen_US
dc.subjectMolecular Dynamic Simulationen_US
dc.titleDiscovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II?en_US
dc.typeArticleen_US

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