Khan Rais Ahmad, de Almeida Andreia, Al-Farhan Khalid, Alsalme Ali, Casini Angela, Ghazzali Mohamed, Reedijk Jan
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
J Inorg Biochem. 2016 Dec;165:128-135. doi: 10.1016/j.jinorgbio.2016.07.001. Epub 2016 Jul 7.
New first-row transition-metal compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) are reported. The compounds have the general formula M(LL)(Hnor)(NO) (M=Co, Ni, Cu, Zn; LL=2,2'-bipyridyl (bpy), 1,10-phenanthroline (phen)) and have been characterized by physical and analytical methods. X-ray structural analysis revealed that the compound of formula [Cu(phen)(Hnor)(NO)], (1) has a distorted 6-coordinated octahedrally-based geometry, with a planar-based [CuNO] core, where Cu-L varies between 1.99 and 2.04Å and two weak axial CuO contacts (2.209 and 2.644Å) from two different nitrates. Based on spectroscopic similarities, the other compounds appear to have the same or very similar coordination geometries. The compounds showed clear cell growth inhibitory effects in two different cancer cell lines in vitro, with the copper and zinc complexes being the most toxic and in fact almost comparable to cisplatin. Flow-cytometry analysis confirmed induction of apoptosis in cancer cells treated with the compounds. Interestingly, co-incubation of the cells with metal complexes and CuCl induced an increase in the cytotoxic effects, most likely due to the conversion of the metal compounds in the corresponding, and most active, copper analogues.
报道了新型的含有去氢骆驼蓬碱配体（9H-吡啶并[3,4-b]吲哚；Hnor）的第一排过渡金属化合物。这些化合物的通式为M(LL)(Hnor)(NO)（M = Co、Ni、Cu、Zn；LL = 2,2'-联吡啶（bpy）、1,10-菲咯啉（phen）），并已通过物理和分析方法进行了表征。X射线结构分析表明，式[Cu(phen)(Hnor)(NO)]的化合物（1）具有扭曲的基于八面体的六配位几何结构，其核心为平面型的[CuNO]，其中Cu-L的距离在1.99至2.04Å之间，并且来自两种不同硝酸盐的两个弱轴向CuO接触（2.209和2.644Å）。基于光谱相似性，其他化合物似乎具有相同或非常相似的配位几何结构。这些化合物在体外对两种不同的癌细胞系显示出明显的细胞生长抑制作用，其中铜和锌配合物毒性最大，实际上几乎与顺铂相当。流式细胞术分析证实了用这些化合物处理的癌细胞中诱导了细胞凋亡。有趣的是，细胞与金属配合物和CuCl共同孵育会导致细胞毒性作用增加，这很可能是由于金属化合物转化为相应的、最具活性的铜类似物所致。
