n--(10h-indolo(3-2-b)quinolin-11-yl)-n-n-dimethylpropane-1-3-diamine and Uterine-Cervical-Neoplasms

n--(10h-indolo(3-2-b)quinolin-11-yl)-n-n-dimethylpropane-1-3-diamine has been researched along with Uterine-Cervical-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for n--(10h-indolo(3-2-b)quinolin-11-yl)-n-n-dimethylpropane-1-3-diamine and Uterine-Cervical-Neoplasms

ArticleYear
Discovery of Novel Schizocommunin Derivatives as Telomeric G-Quadruplex Ligands That Trigger Telomere Dysfunction and the Deoxyribonucleic Acid (DNA) Damage Response.
    Journal of medicinal chemistry, 2018, 04-26, Volume: 61, Issue:8

    Telomeric G-quadruplex targeting and telomere maintenance interference are emerging as attractive strategies for anticancer therapies. Here, a novel molecular 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 biophysical assay. The cytotoxicity of the derivatives toward cancer cell lines was evaluated by the methyl 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.

    Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; DNA; DNA Damage; Drug Discovery; Female; G-Quadruplexes; G2 Phase Cell Cycle Checkpoints; Humans; Indoles; Ligands; Mice, Inbred BALB C; Telomerase; Telomere; Telomere Shortening; Telomere-Binding Proteins; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

2018