Das, Tania ; Panda, Deepanjan ; Saha, Puja ; Dash, Jyotirmayee (2018) Small Molecule Driven Stabilization of Promoter G-Quadruplexes and Transcriptional Regulation of c-MYC Bioconjugate Chemistry, 29 (8). pp. 2636-2645. ISSN 1043-1802
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Official URL: http://doi.org/10.1021/acs.bioconjchem.8b00338
Related URL: http://dx.doi.org/10.1021/acs.bioconjchem.8b00338
Abstract
G-quadruplexes have been considered attractive therapeutic targets for the development of anticancer agents. We herein report synthesis of a series of carbazole derivatives by employing modular one-pot Cu(I) catalyzed cycloaddition. These carbazole derivatives are easily synthesizable, soluble in aqueous media, and able to strongly interact with quadruplexes. FRET based melting assay and fluorescence titration experiments suggest that a carbazole derivative, Cz-1, preferentially binds c-MYC quadruplex DNA over other investigated quadruplex and duplex DNAs. The biological studies revealed that Cz-1 inhibits cancer cell proliferation by inducing apoptosis. Moreover, Cz-1 inhibits the expression of c-MYC at transcriptional as well as translational levels. Exon-specific-assay confirms that the downregulation of MYC expression is mainly driven by the binding of Cz-1 with the promoter G-quadruplex structures. Immunocytochemistry, using quadruplex binding antibody BG4, further suggests that Cz-1 induces and stabilizes G-quadruplexes in a cellular system.
Item Type: | Article |
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Source: | Copyright of this article belongs to AI2. |
ID Code: | 126648 |
Deposited On: | 17 Oct 2022 05:43 |
Last Modified: | 17 Oct 2022 05:43 |
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