Pyrazolyl-Benzoxazinone Derivatives as Dual Hsp Inhibitors in Human Breast Cancer

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dc.authoridTUTAR, Yusuf/0000-0003-2613-9644
dc.authoridKOCA, IRFAN/0000-0001-7873-159X
dc.authoridSERT, YUSUF/0000-0001-8836-8667
dc.contributor.authorKoca, Irfan
dc.contributor.authorKamaci, Volkan
dc.contributor.authorOzsoy, Ceylan
dc.contributor.authorSert, Yusuf
dc.contributor.authorKani, Ibrahim
dc.contributor.authorTutar, Lutfi
dc.contributor.authorTutar, Yusuf
dc.date.accessioned2024-10-26T18:11:04Z
dc.date.available2024-10-26T18:11:04Z
dc.date.issued2022
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractHeat Shock Proteins (Hsps) play major role on the onset of several cancers. Metabolic rates of cancer cells are higher compared to that of untransformed cells. This accelerated rate force functional substrate proteins to fold faster than normal folding rate. Although, the process leads cell cycle halting and eventually induces apoptosis, Hsps help cell survival and inhibit apoptosis and fold substrate proteins especially signaling proteins. When cancer cells accelerate the metabolism for invasion and metastasis, substrate proteins must fold to their native state rapidly. Since, functional forms of the proteins must be folded properly, cancer cells overexpress Hsps to fold substrate proteins and avoid apoptosis. Hsp90 and Hsp70 play key role in these processes. Inhibition of either Hsp90 or Hsp70 display complementary function. Therefore, dual inhibition of Hsp70 and Hsp90 potentially provides anticancer affect. In silico studies showed that pyrazolyl-benzoxazine derivatives display binding activity for both Hsps. For this purpose, pyrazole-3-carbonyl chloride were converted to pyrazolyl-benzoxazine derivatives via reactions of anthranilic acids in good yields (68-83 %). The structures of the newly synthesized compounds were elucidated by IR-NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. Binding of the compounds inhibit function of Hsps and cause cytotoxic effect over MCF-7 cells. The compounds display potential anticancer effects.
dc.description.sponsorshipScience and Technology Practice & Research Centre of Yozgat Bozok University [2015 FBE/T167]; Turkish National Academy of Sciences
dc.description.sponsorshipSynthesis studies were carried out within the scope of Volkan Kamac's master's thesis studies.[31] For characterization, relevant corresponding spectra (IR, NMR) can be found in the related thesis. This work was funded through a seed grand from Science and Technology Practice & Research Centre of Yozgat Bozok University (Project No: 2015 FBE/T167) and Turkish National Academy of Sciences for YT. The authors gratefully acknowledge the Medicinal Plants and Medicine Research Centre of Anadolu University, Eskiehir, Turkey, for the use of X-ray Diffractometer.
dc.identifier.doi10.1002/slct.202200359
dc.identifier.issn2365-6549
dc.identifier.issue19
dc.identifier.scopus2-s2.0-85130289279
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1002/slct.202200359
dc.identifier.urihttps://hdl.handle.net/20.500.12418/30496
dc.identifier.volume7
dc.identifier.wosWOS:000797693900002
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectBenzoxazine
dc.subjectBreast Cancer
dc.subjectHSP
dc.subjectMolecular Docking
dc.subjectPyrazole
dc.titlePyrazolyl-Benzoxazinone Derivatives as Dual Hsp Inhibitors in Human Breast Cancer
dc.typeArticle

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