Fatma Khushnood, Thumpati Prasanth, Panda Deepanjan, Velayutham Ravichandiran, Dash Jyotirmayee
Indian Association for the Cultivation of Science, 2A & 2B, Raja Subodh Chandra Mallick Road, Jadavpur, Kolkata-700032, India.
National Institute of Pharmaceutical Education and Research, Chunilal Bhawan, Maniktala, Kolkata-700054, India.
ACS Med Chem Lett. 2024 Feb 12;15(3):388-395. doi: 10.1021/acsmedchemlett.3c00537. eCollection 2024 Mar 14.
In this study, carbazole () and dibenzofuran () derivatives were synthesized to examine their effect on the biomolecular recognition of G-quadruplex (G4) targets. Biophysical studies revealed that , a carbazole derivative, exhibits a specific affinity and effectively stabilizes the G4. Molecular modeling suggests a stable interaction of with the terminal G-tetrad of G4. Biological studies demonstrate that efficiently enters cells, reduces gene expression, and induces cell cycle arrest, DNA damage, and apoptosis in cancer cells. These findings demonstrate as a selective G4 ligand with therapeutic potential, providing insight into the structural basis of its anticancer mechanisms.
在本研究中，合成了咔唑（）和二苯并呋喃（）衍生物，以研究它们对G-四链体（G4）靶点生物分子识别的影响。生物物理研究表明，咔唑衍生物表现出特异性亲和力，并能有效稳定G4。分子模拟表明与G4的末端G-四联体存在稳定相互作用。生物学研究证明能有效进入细胞，降低基因表达，并诱导癌细胞的细胞周期停滞、DNA损伤和凋亡。这些发现表明是一种具有治疗潜力的选择性G4配体，为其抗癌机制的结构基础提供了见解。
