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利用苯并咪唑基席夫碱配合物与 l-组氨酸作为共配体的生物学功效:联合分子对接、DNA 相互作用、抗菌和细胞毒性研究。

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.

机构信息

Research Department of Chemistry, VHNSN College, Virudhunagar 626 001, India.

Research Department of Chemistry, VHNSN College, Virudhunagar 626 001, India.

出版信息

Bioorg Chem. 2018 Apr;77:269-279. doi: 10.1016/j.bioorg.2018.01.024. Epub 2018 Feb 3.

DOI:10.1016/j.bioorg.2018.01.024
PMID:29421702
Abstract

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 (HO). 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.

摘要

四种新的金属配合物被合成,并在初步的 DNA 结合研究得到充分证实后,对其细胞毒性进行了筛选。金属配合物可以通过嵌入结合模式与 CT-DNA 结合。这也通过分子对接研究得到了证实。这些配合物与 pBR322 DNA 的 DNA 切割效率通过凝胶电泳进行了研究。在氧化剂 (HO) 的存在下,这些配合物被发现能够促进 pBR322 DNA 从超螺旋形式 I 向开环形式 II 的切割。与顺铂相比,研究的配合物的体外化学敏感性表现出显著的细胞毒性作用。这些发现代表了对这些配合物与细胞增殖中基本重要的其他细胞成分的可能相互作用的探索。体外抗癌活性表明,Cu(II) 配合物对所选的人类肿瘤细胞系具有活性,并且体外抗癌活性的顺序与 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,所有配合物都被发现对癌细胞系具有细胞毒性作用,其效力超过广泛使用的药物顺铂,因此它们有可能成为有前途的抗癌药物。引人注目的是,它们对正常细胞淋巴细胞没有毒性,这表明它们只选择性地杀死癌细胞。

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