School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147001, India.
School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147001, India.
Bioorg Chem. 2020 Mar;96:103631. doi: 10.1016/j.bioorg.2020.103631. Epub 2020 Feb 7.
The synthesis and characterization of a series of naphthalimide and phenanthro[9,10-d]imidazole conjugate is described. These compounds are evaluated in vitro for their cytotoxicity towards 60 human cancer cell lines. Derivative 16 shows excellent cytotoxic activity against these cancer cell lines with the range of growth inhibition from -55.78 to 94.53. The most potent derivative (ethylpiperazine, 16) is further studied to evaluate the interaction with ct-DNA using absorption and emission spectroscopy as well as DNA viscosity measurement. The DNA binding studies indicate that compound 16 is significantly interacted with DNA through groove binding having binding constant value of 7.81 × 10 M alongwith partial intercalation between the base pairs of DNA strands. Further, topoisomerase inhibition study suggests that compound 16 is induced apoptosis and inhibits human topoisomerase (Topo-IIα) as a possible intracellular target. Molecular docking study of compound 16 with ct-DNA shows good docking score.
描述了一系列萘酰亚胺和菲并[9,10-d]咪唑共轭物的合成和表征。这些化合物在体外对 60 个人类癌细胞系的细胞毒性进行了评估。衍生物 16 对这些癌细胞系表现出优异的细胞毒性活性，生长抑制范围为-55.78 至 94.53。最有效的衍生物（乙基哌嗪，16）进一步研究，以评估与 ct-DNA 的相互作用，使用吸收和发射光谱以及 DNA 粘度测量。DNA 结合研究表明，化合物 16 通过沟槽结合与 DNA 发生显著相互作用，具有 7.81×10 M 的结合常数，同时在 DNA 链碱基对之间进行部分嵌入。此外，拓扑异构酶抑制研究表明，化合物 16 诱导细胞凋亡并抑制人拓扑异构酶（Topo-IIα）作为可能的细胞内靶标。化合物 16 与 ct-DNA 的分子对接研究显示出良好的对接分数。
