Department of Chemistry, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
Eur J Med Chem. 2011 Feb;46(2):659-69. doi: 10.1016/j.ejmech.2010.11.046. Epub 2010 Dec 8.
Inhibitors of topoisomerase I constitute a novel family of antitumor agents. The class of benzimidazole derivatives contains compounds possessing affinity to DNA. For example, fluorescent stains Hoechst 33342 and Hoechst 33258 interact with DNA as ligand and produce nonspecific inhibition of the catalytic activity of many enzymes involved in DNA synthesis, including DNA topoisomerase and DNA helicase. Several 2-aryl-5-substituted-2,5-bisbenzimidazole derivatives were synthesized and ability of these derivatives to induce DNA cleavage in the presence of topoisomerase I was evaluated in vitro. These analogs were also assayed for their cytotoxicity against U87, MCF7 and HeLa human tumor cells. All the four compounds showed a potent growth inhibitory effect on all the cell lines, with IC50 in the μM range.
拓扑异构酶 I 抑制剂构成了一类新型的抗肿瘤药物。苯并咪唑衍生物类包含具有与 DNA 亲和力的化合物。例如，荧光染料 Hoechst 33342 和 Hoechst 33258 与 DNA 作为配体相互作用，并产生对许多参与 DNA 合成的酶（包括 DNA 拓扑异构酶和 DNA 解旋酶）的非特异性催化活性抑制。合成了几种 2-芳基-5-取代的 2,5-双苯并咪唑衍生物，并在体外评估了这些衍生物在存在拓扑异构酶 I 的情况下诱导 DNA 断裂的能力。还对这些类似物针对 U87、MCF7 和 HeLa 人肿瘤细胞的细胞毒性进行了检测。所有这四种化合物对所有细胞系均显示出很强的生长抑制作用，IC50 在 μM 范围内。
