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银吡啶-2-磺酸络合物 - 其表征、DNA 结合、拓扑异构酶 I 抑制、抗菌和抗癌反应。

Silver pyridine-2-sulfonate complex - its characterization, DNA binding, topoisomerase I inhibition, antimicrobial and anticancer response.

机构信息

Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.

Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.

出版信息

J Inorg Biochem. 2018 Sep;186:206-216. doi: 10.1016/j.jinorgbio.2018.06.006. Epub 2018 Jun 18.

Abstract

In the current study the ability of silver pyridine-2-sulfonate complex to exert multiple biological activities is compared with the pharmacological action of silver sulfadiazine (AgSD). Polymeric form of {[Ag(py-2-SO)]} (AgPS) was synthesized and characterized by analytical techniques (IR, CHN, TG/DTA, MS) and its molecular formula was established. The crystal structure was determined by X-ray diffraction method and the polymeric complex crystallizes in the triclinic P-1 space group. The stability of Ag(I) complex was verified by H and C NMR measurements and the interaction with calf thymus DNA through UV-VIS and fluorescence quenching experiments was studied. The Ag(I) complex was able to interact with DNA by dual binding mode: partial intercalation along groove binding. The binding constants were calculated to be in the order of 10 M. Topoisomerase I inhibition study have shown that silver complex is inhibiting its activity at concentration of 30 μM. The cytotoxic activity of AgPS and AgSD against mouse leukaemia L1210 S, R and T cell line was also evaluated. AgPS showed higher cytotoxicity than AgSD after 48 h incubation. The results suggest that mechanism of cell death is necrosis with a contribution of late apoptosis. Antimicrobial testing indicates higher growth inhibition effect of AgPS with comparison to commercially available AgSD.

摘要

在本研究中,比较了吡啶-2-磺酸银配合物发挥多种生物学活性的能力与磺胺嘧啶银(AgSD)的药理作用。通过分析技术(IR、CHN、TG/DTA、MS)合成并表征了{[Ag(py-2-SO)]}(AgPS)的聚合物形式,并建立了其分子式。通过 X 射线衍射法确定了晶体结构,聚合物配合物在三斜 P-1 空间群中结晶。通过 1H 和 13C NMR 测量验证了 Ag(I)配合物的稳定性,并通过紫外-可见和荧光猝灭实验研究了其与小牛胸腺 DNA 的相互作用。Ag(I)配合物能够通过双重结合模式与 DNA 相互作用:部分嵌入沿沟结合。计算了结合常数,其顺序为 10 M。拓扑异构酶 I 抑制研究表明,银配合物在 30 μM 的浓度下抑制其活性。还评估了 AgPS 和 AgSD 对小鼠白血病 L1210 S、R 和 T 细胞系的细胞毒性。与 48 小时孵育后相比,AgPS 显示出比 AgSD 更高的细胞毒性。结果表明,细胞死亡的机制是坏死,并伴有晚期凋亡。抗菌测试表明,与市售的 AgSD 相比,AgPS 具有更高的生长抑制作用。

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