A serial of naphthalenebenzimidizole-Pt complexes 1-6 were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that complexes 1-6 exhibited moderate to high antiproliferative activity against Hela, HepG2, SKOV-3, NCI-H460, BEL-7404 and A549 cancer cell lines, while they displayed obvious sensitivity and selectivity against SMMC-7721 and U251 cell lines and low toxicity against normal HL-7702 cells, in comparison with cisplatin. In vivo antitumor assay results indicated that complex 1 and 5 exhibited important in vivo antiproliferative activity in the NCI-460 and SMMC-7721 models, in comparison with cisplatin, respectively. Complexes 1 and 5 exhibited better antiproliferative activity against A549CDDP and SKOV3CDDP cell lines than cisplatin, with IC50 values of 6.98 ± 0.47 μM, 5.62 ± 0.88 μM and 13.13 ± 2.11 μM, 5.30 ± 0.33 μM, respectively, while they displayed potential antiproliferation against A549 and SKOV3 cell lines, with IC50 values of 7.32 ± 0.51 μM, 5.19 ± 0.49 μM and 14.92 ± 0.11 μM, 12.19 ± 0.92 μM, indicating the introduction of naphthalenebenzimidizole into platinum-metal system may overcome the resistance. Mechanistic studies showed that the representative complexes 1 and 5 exerted the antitumor effect mainly by the obvious covalent binding with DNA and the upregulation of the expression level of intracellular topo I, showing different action mechanism from cisplatin.

中文翻译：

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萘苯并咪唑铂（II）配合物作为潜在抗肿瘤剂的设计，合成和生物学评估。

设计并合成了一系列萘苯并咪唑-Pt配合物1-6作为抗肿瘤剂。体外抗肿瘤试验结果表明，复合物1-6对Hela，HepG2，SKOV-3，NCI-H460，BEL-7404和A549癌细胞具有中等至较高的抗增殖活性，而它们对SMMC-7721则具有明显的敏感性和选择性。和顺铂相比，U251和U251细胞系对正常的HL-7702细胞毒性低。体内抗肿瘤测定结果表明，与顺铂相比，复合物1和5在NCI-460和SMMC-7721模型中分别具有重要的体内抗增殖活性。与顺铂相比，复合物1和5对A549CDDP和SKOV3CDDP细胞系表现出更好的抗增殖活性，IC50值分别为6.98±0.47μM，5.62±0.88μM和13.13±2.11μM，5。分别为30±0.33μM，对A549和SKOV3细胞系具有潜在的抗增殖作用，IC50值分别为7.32±0.51μM，5.19±0.49μM和14.92±0.11μM，12.19±0.92μM，表明将萘苯并咪唑引入铂中-金属系统可以克服阻力。机理研究表明，典型的复合物1和5主要通过与DNA的明显共价结合以及细胞内topo I表达水平的上调而发挥抗肿瘤作用，显示出与顺铂不同的作用机理。表明将萘苯并咪唑引入铂-金属体系中可能会克服该阻力。机理研究表明，典型的复合物1和5主要通过与DNA的明显共价结合以及细胞内topo I表达水平的上调而发挥抗肿瘤作用，显示出与顺铂不同的作用机理。表明将萘苯并咪唑引入铂-金属体系可能会克服该阻力。机理研究表明，典型的复合物1和5主要通过与DNA的明显共价结合以及细胞内topo I表达水平的上调而发挥抗肿瘤作用，显示出与顺铂不同的作用机理。