INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX

ABSTRACT Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc G-quadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly wi...

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Autores principales:	Mi,Ya-Xuan, Wang,Shuang, Yan,Shuang-Mei, Cui,Yue, Wang,Ming-He, Zheng,Ze-Bao, Zhao,Xiao-Long
Lenguaje:	English
Publicado:	Sociedad Chilena de Química 2019
Materias:	Ruthenium c-myc G-quadruplex DNA Topoisomerase Cytotoxicity
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072019000404639
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spelling	oai:scielo:S0717-970720190004046392020-02-03INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEXMi,Ya-XuanWang,ShuangYan,Shuang-MeiCui,YueWang,Ming-HeZheng,Ze-BaoZhao,Xiao-Long Ruthenium c-myc G-quadruplex DNA Topoisomerase Cytotoxicity ABSTRACT Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc G-quadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly with constants of 1.18 × 107 (Pu27) and 4.13 × 106 M-1 (Pu22) via groove mode as determined from absorption and luminescence titrations, as well as CD spectra. Results of continuous variation analysis confirmed that the complex interacted with c-myc G-quadruplex DNA through a 1:1 binding stoichiometry. As verified by PCR-stop assay, the replication of c-myc DNA was effectively blocked by the complex with the complete inhibition at the complex concentration of 4.0 μM both for Pu27 and Pu22, suggesting that the complex could efficiently induce the formation of c-myc G-quadruplex DNA. The appearance of blue TMB solution in the visual experiment also proved that the sequences of Pu27 and Pu22 could fold into G-quadruplex under the induction of the complex. Nevertheless, the complex was found to exhibit weak stabilization ability on c-myc G-quadruplex DNA according to FRET assay, which increased the melting point of c-myc DNA only 3-3.5 °C. The experiments on Topoisomerase inhibition and cytotoxicity of the complex showed that it acted as an inhibitor of TopoI and exhibited moderate anticancer activity against MCF-7 and Huh-7 tumor cells.info:eu-repo/semantics/openAccessSociedad Chilena de QuímicaJournal of the Chilean Chemical Society v.64 n.4 20192019-12-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072019000404639en10.4067/S0717-97072019000404639
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Ruthenium c-myc G-quadruplex DNA Topoisomerase Cytotoxicity
spellingShingle	Ruthenium c-myc G-quadruplex DNA Topoisomerase Cytotoxicity Mi,Ya-Xuan Wang,Shuang Yan,Shuang-Mei Cui,Yue Wang,Ming-He Zheng,Ze-Bao Zhao,Xiao-Long INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
description	ABSTRACT Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc G-quadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly with constants of 1.18 × 107 (Pu27) and 4.13 × 106 M-1 (Pu22) via groove mode as determined from absorption and luminescence titrations, as well as CD spectra. Results of continuous variation analysis confirmed that the complex interacted with c-myc G-quadruplex DNA through a 1:1 binding stoichiometry. As verified by PCR-stop assay, the replication of c-myc DNA was effectively blocked by the complex with the complete inhibition at the complex concentration of 4.0 μM both for Pu27 and Pu22, suggesting that the complex could efficiently induce the formation of c-myc G-quadruplex DNA. The appearance of blue TMB solution in the visual experiment also proved that the sequences of Pu27 and Pu22 could fold into G-quadruplex under the induction of the complex. Nevertheless, the complex was found to exhibit weak stabilization ability on c-myc G-quadruplex DNA according to FRET assay, which increased the melting point of c-myc DNA only 3-3.5 °C. The experiments on Topoisomerase inhibition and cytotoxicity of the complex showed that it acted as an inhibitor of TopoI and exhibited moderate anticancer activity against MCF-7 and Huh-7 tumor cells.
author	Mi,Ya-Xuan Wang,Shuang Yan,Shuang-Mei Cui,Yue Wang,Ming-He Zheng,Ze-Bao Zhao,Xiao-Long
author_facet	Mi,Ya-Xuan Wang,Shuang Yan,Shuang-Mei Cui,Yue Wang,Ming-He Zheng,Ze-Bao Zhao,Xiao-Long
author_sort	Mi,Ya-Xuan
title	INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
title_short	INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
title_full	INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
title_fullStr	INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
title_full_unstemmed	INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX
title_sort	induction of c-myc g-quadruplex dna and cytotoxicity of a calix[]arene-containing binuclear ruthenium(ii) complex
publisher	Sociedad Chilena de Química
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072019000404639
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INDUCTION OF C-MYC G-QUADRUPLEX DNA AND CYTOTOXICITY OF A CALIX[]ARENE-CONTAINING BINUCLEAR RUTHENIUM(II) COMPLEX

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