Design, synthesis, biological evaluation and molecular docking of novel molecules to PARP-1 enzyme

Basit Öğe Kaydı
dc.contributor.authorTok, Fatih
dc.contributor.authorKaymakçıoğlu Bedia
dc.contributor.authorİlhan, Recep
dc.contributor.authorYılmaz, Sinem
dc.contributor.authorBallar Kırmızıbayrak, Petek
dc.contributor.authorTaşkın Tok, Tuğba
dc.date.accessioned2021-02-19T21:20:46Z
dc.date.available2021-02-19T21:20:46Z
dc.date.issued2019
dc.departmentALKÜ
dc.description.abstractPoly (ADP-ribose) polymerase (PARP) enzyme catalyzes the transfer of ADP-ribose into target proteins. Therefore, PARP is responsible for DNA repair, cell proliferation, and cell death. In this study, potential PARP enzyme inhibitors were designed and synthesized. The synthesized compounds were elucidated by Fourier-transform infrared spectroscopy, 1 H NMR, 13 C NMR, heteronuclear single-quantum correlation, and mass spectrometry, and their purity was checked via thin-layer chromatography, high-performance liquid chromatography, and elemental analysis. A total of 63 newly synthesized compounds were screened in terms of PARP inhibition by cellular PARylation assay in the HeLa cell line. It was found that 19 compounds significantly inhibited the H 2 O 2 -induced cellular PARylation. The chemosensitizer effect of these compounds in cancer cells treated with doxorubicin (doxo) was investigated. It was found that the combination of potent PARP inhibitors with doxo potentiated a cytotoxic effect, similar to that of olaparib. The results of the molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that compound 60 might be classified as a potential PARP inhibitor candidate. Taken together, all of the results suggested that carbohydrazide derivatives could be a promising lead for the treatment for cancer disorders. © TÜBİTAK
dc.description.sponsorshipSAG-C-DRP-100616-0260 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK 215S112
dc.description.sponsorshipThis study was supported by the Scientific and Technical Research Council of Turkey (TÜBİTAK) Research Fund under project number: 215S112 and the Marmara University Scientific Research Commission under grant number: SAG-C-DRP-100616-0260.
dc.identifier.doi10.3906/kim-1905-15
dc.identifier.endpage1305en_US
dc.identifier.issn1300-0527
dc.identifier.issue5en_US
dc.identifier.scopusqualityQ3
dc.identifier.startpage1290en_US
dc.identifier.urihttps://doi.org/10.3906/kim-1905-15
dc.identifier.urihttps://hdl.handle.net/20.500.12868/674
dc.identifier.volume43en_US
dc.indekslendigikaynakScopus
dc.institutionauthor0-belirlenecek
dc.language.isoen
dc.publisherTUBITAK
dc.relation.ispartofTurkish Journal of Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectADMET
dc.subjectCarbohydrazide
dc.subjectMolecular docking
dc.subjectPARP inhibitors
dc.subjectUrea
dc.titleDesign, synthesis, biological evaluation and molecular docking of novel molecules to PARP-1 enzyme
dc.typeArticle

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