Toward the Development of Specific G-Quadruplex Binders: Synthesis, Biophysical, and Biological Studies of New Hydrazone Derivatives
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- 作者：Jussara Amato ; Rita Morigi ; Bruno Pagano ; Alessia Pagano ; Stephan Ohnmacht ; Alessio De Magis ; Yee-Peng Tiang ; Giovanni Capranico ; Alessandra Locatelli ; Alessandra Graziadio ; Alberto Leoni ; Mirella Rambaldi ; Ettore Novellino ; Stephen Neidle ; Antonio Randazzo
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：June 23, 2016
- 年：2016
- 卷：59
- 期：12
- 页码：5706-5720
- 全文大小：712K
- 年卷期：0
- ISSN：1520-4804
文摘
G-Quadruplex-binding compounds are currently perceived as possible anticancer therapeutics. Here, starting from a promising lead, a small series of novel hydrazone-based compounds were synthesized and evaluated as G-quadruplex binders. The in vitro G-quadruplex-binding properties of the synthesized compounds were investigated employing both human telomeric and oncogene promoter G-quadruplexes with different folding topologies as targets. The present investigation led to the identification of potent G-quadruplex stabilizers with high selectivity over duplex DNA and preference for one G-quadruplex topology over others. Among them, selected derivatives have been shown to trap G-quadruplex structures in the nucleus of cancer cells. Interestingly, this behavior correlates with efficient cytotoxic activity in human osteosarcoma and colon carcinoma cells.