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Exploiting the biological efficacy of benzimidazole based Schiff base complexes with l-Histidine as a co-ligand: Combined molecular docking, DNA interaction, antimicrobial and cytotoxic studies
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2018-02-03 , DOI: 10.1016/j.bioorg.2018.01.024
Ganesan Kumaravel , Ponnukalai Ponya Utthra , Natarajan Raman

Four new metal complexes were synthesized and screened for their cytotoxic activity after sufficient assertion from the preliminary DNA binding studies. The metal complexes could bind to CT-DNA through intercalation binding mode. This has also been confirmed by the molecular docking studies. The DNA cleavage efficiencies of these complexes with pBR322 DNA were investigated by gel electrophoresis. The complexes were found to promote the cleavage of pBR322 DNA from the supercoiled form I to the open circular form II in the presence of an oxidizing agent (H2O2). The in vitro chemosensitivity of the studied complexes exhibits significant cytotoxic effects, compared to those reported for cisplatin. These findings represent a prompting to search for the probable interaction of these complexes with other cellular elements of fundamental consequence in cell proliferation. The in vitro anticancer activities indicate that the Cu(II) complex is active against the selected human tumor cell lines, and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. Towards noncancerous cell line, Cu(II) complex exhibits very low toxicity. On the other hand all the complexes have been found to exhibit cytotoxic effects against cancerous cell lines with potency more than that of the widely used drug cisplatin and hence they have the potential to act as promising anticancer agents. Captivatingly, they are non-toxic to normal cell lymphocytes revealing that they are selective in killing only the cancer cells.



中文翻译:

利用基于苯并咪唑的席夫碱配合物与l-组氨酸作为共配体的生物学功效:分子对接,DNA相互作用,抗微生物和细胞毒性研究相结合

从初步的DNA结合研究充分论证后,合成了四种新的金属配合物,并筛选了它们的细胞毒活性。金属配合物可以通过插层结合方式与CT-DNA结合。分子对接研究也证实了这一点。通过凝胶电泳研究了这些与pBR322 DNA的复合物的DNA切割效率。发现该复合物在存在氧化剂(H 2 O 2)的情况下促进了pBR322 DNA从超螺旋形式I向开环形式II的切割。在体外与报道的顺铂相比,所研究复合物的化学敏感性表现出显着的细胞毒性作用。这些发现提示寻找这些复合物与可能对细胞增殖产生根本影响的其他细胞成分相互作用的提示。的体外抗癌活性表明,铜(II)配合物是针对所选择的人类肿瘤细胞系的活性,和顺序在体外抗癌活性与DNA结合亲和力一致。对于非癌细胞系,Cu(II)配合物表现出非常低的毒性。另一方面,已经发现所有复合物对癌细胞系均具有比广泛使用的顺铂药物更强的细胞毒性作用,因此它们有潜力用作有希望的抗癌药。令人着迷的是,它们对正常细胞的淋巴细胞无毒,表明它们在仅杀死癌细胞方面具有选择性。

更新日期:2018-02-03
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