Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction.

التفاصيل البيبلوغرافية
العنوان:	Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction.
المؤلفون:	Ribeiro GH; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Guedes APM; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., de Oliveira TD; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., de Correia CRSTB; Departamento de Genética e Evolução, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Colina-Vegas L; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil.; Instituto de Química, Universidade Federal do Rio Grande do Sul, CP 15003, 91501-970 Porto Alegre, Rio Grande do Sul, Brazil., Lima MA; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Nóbrega JA; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Cominetti MR; Departamento de Gerontologia, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo Brazil., Rocha FV; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Ferreira AG; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Castellano EE; Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, São Paulo, Brazil., Teixeira FR; Departamento de Genética e Evolução, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil., Batista AA; Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, São Paulo, Brazil.
المصدر:	Inorganic chemistry [Inorg Chem] 2020 Oct 19; Vol. 59 (20), pp. 15004-15018. Date of Electronic Publication: 2020 Sep 30.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 0366543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-510X (Electronic) Linking ISSN: 00201669 NLM ISO Abbreviation: Inorg Chem Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: [Easton, Pa.] American Chemical Society.
مواضيع طبية MeSH:	Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , DNA Topoisomerases, Type I/metabolism , Proteasome Inhibitors/pharmacology , Topoisomerase I Inhibitors/*pharmacology, Antineoplastic Agents/chemical synthesis ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Coordination Complexes/chemical synthesis ; Drug Screening Assays, Antitumor ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Phosphines/chemical synthesis ; Phosphines/pharmacology ; Proteasome Inhibitors/chemical synthesis ; Ruthenium/chemistry ; Sulfhydryl Compounds/chemical synthesis ; Sulfhydryl Compounds/pharmacology ; Topoisomerase I Inhibitors/chemical synthesis
مستخلص:	In this paper, a series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF 6 ( Ru1 - Ru3 ), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, Ru1 ), 2-mercaptopyrimidine (pySm, Ru2 ), and 4,6-diamino-2-mercaptopyrimidine (damp, Ru3 ), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental analysis, spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and X-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their respective aromatic hydrogen atoms of the compounds in the assignment stands outs, by ¹ H- ³¹ P HMBC experiments. The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clinical drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10A (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle analysis upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Additionally, the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was investigated, and the biomolecules were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomolecule in the pharmacokinetics of drugs, human serum albumin. The experimental results indicate that the complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex Ru3 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent.
المشرفين على المادة:	0 (Antineoplastic Agents) 0 (Coordination Complexes) 0 (Phosphines) 0 (Proteasome Inhibitors) 0 (Sulfhydryl Compounds) 0 (Topoisomerase I Inhibitors) 7UI0TKC3U5 (Ruthenium) EC 5.99.1.2 (DNA Topoisomerases, Type I) EC 5.99.1.2 (TOP1 protein, human)
تواريخ الأحداث:	Date Created: 20200930 Date Completed: 20210517 Latest Revision: 20210517
رمز التحديث:	20240628
DOI:	10.1021/acs.inorgchem.0c01835
PMID:	32997499
قاعدة البيانات:	MEDLINE

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تدمد:	1520-510X
DOI:	10.1021/acs.inorgchem.0c01835