دورية أكاديمية
Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity.
العنوان: | Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity. |
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المؤلفون: | Nimbarte VD; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany., Wirmer-Bartoschek J; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany., Gande SL; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany.; German Cancer Research Center and German Cancer Consortium, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Alshamleh I; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany., Seibert M; Department of Medicine 2, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Nasiri HR; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany., Schnütgen F; German Cancer Research Center and German Cancer Consortium, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Department of Medicine 2, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Serve H; German Cancer Research Center and German Cancer Consortium, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Department of Medicine 2, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Schwalbe H; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Straße 7, 60438, Frankfurt am Main, Germany.; German Cancer Research Center and German Cancer Consortium, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Frankfurt Cancer Institute (FCI), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany. |
المصدر: | ChemMedChem [ChemMedChem] 2021 May 18; Vol. 16 (10), pp. 1667-1679. Date of Electronic Publication: 2021 Mar 22. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101259013 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1860-7187 (Electronic) Linking ISSN: 18607179 NLM ISO Abbreviation: ChemMedChem Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Weinheim, Germany : Wiley-VCH, c2006- |
مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , G-Quadruplexes/*drug effects , Genes, myc/*drug effects , Indoles/*pharmacology, Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; HeLa Cells ; Humans ; Indoles/chemical synthesis ; Indoles/chemistry ; Molecular Structure ; Structure-Activity Relationship ; Tumor Cells, Cultured |
مستخلص: | Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5'- and 3'-ends) in a 2 : 1 stoichiometry. (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.) |
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معلومات مُعتمدة: | SFB1177 Deutsche Forschungsgemeinschaft; SCHN1166/4-1 Deutsche Forschungsgemeinschaft |
فهرسة مساهمة: | Keywords: G-quadruplex binders; c-Myc; nitroindoles; oncogene promoters, reactive oxygen species, structure-activity relationships |
المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Indoles) O2BHX6EDBN (5-nitroindole) |
تواريخ الأحداث: | Date Created: 20210128 Date Completed: 20220106 Latest Revision: 20240402 |
رمز التحديث: | 20240402 |
مُعرف محوري في PubMed: | PMC8252724 |
DOI: | 10.1002/cmdc.202000835 |
PMID: | 33508167 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1860-7187 |
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DOI: | 10.1002/cmdc.202000835 |