Discovery of Novel Schizocommunin Derivatives as Telomeric G-Quadruplex Ligands That Trigger Telomere Dysfunction and the Deoxyribonucleic Acid (DNA) Damage Response was written by Che, Tong;Chen, Shuo-Bin;Tu, Jia-Li;Wang, Bo;Wang, Yu-Qing;Zhang, Yan;Wang, Jing;Wang, Zeng-Qing;Zhang, Ze-Peng;Ou, Tian-Miao;Zhao, Yong;Tan, Jia-Heng;Huang, Zhi-Shu. And the article was included in Journal of Medicinal Chemistry in 2018.Reference of 774-47-0 This article mentions the following:
Telomeric G-quadruplex targeting and telomere maintenance interference are emerging as attractive strategies for anticancer therapies. Here, a novel mol. scaffold is explored for telomeric G-quadruplex targeting. A series of novel schizocommunin derivatives was designed and synthesized as potential telomeric G-quadruplex ligands. The interaction of telomeric G-quadruplex DNA with the derivatives was explored by biophys. assay. The cytotoxicity of the derivatives toward cancer cell lines was evaluated by the Me thiazolyl tetrazolium (MTT) assay. Among the derivatives, compound 16 showed great stabilization ability toward telomeric G-quadruplex DNA and good cytotoxicity toward cancer cell lines. Further cellular experiments indicated that 16 could induce the formation of telomeric G-quadruplex in cells, triggering a DNA damage response at the telomere and causing telomere dysfunction. These effects ultimately provoked p53-mediated cell cycle arrest and apoptosis, and suppressed tumor growth in a mouse xenograft model. Our work provides a novel scaffold for the development of telomeric G-quadruplex ligands. In the experiment, the researchers used many compounds, for example, 5,6-Difluoroindoline-2,3-dione (cas: 774-47-0Reference of 774-47-0).
5,6-Difluoroindoline-2,3-dione (cas: 774-47-0) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Moreover, it is known that it controls biofilm formation. However, the role of indole in the cell has not been fully elucidated.Reference of 774-47-0
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