Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
Faculty of Science and Engineering, Universiti Tunku Abdul Rahman, 53300 Kuala Lumpur, Malaysia.
J Inorg Biochem. 2021 Jul;220:111453. doi: 10.1016/j.jinorgbio.2021.111453. Epub 2021 Apr 19.
The cobalt(II), copper(II) and zinc(II) complexes of 1,10-phenanthroline (phen) and maltol (mal) (complexes 1, 2, 3 respectively) were prepared from their respective metal(II) chlorides and were characterized by FT-IR, elemental analysis, UV spectroscopy, molar conductivity, p-nitrosodimethylaniline assay and mass spectrometry. The X-ray structure of a single crystal of the zinc(II) analogue reveals a square pyramidal structure with distinctly shorter apical chloride bond. All complexes were evaluated for their anticancer property on breast cancer cell lines MCF-7 and MDA-MB-231, and normal cell line MCF-10A, using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and morphological studies. Complex 2 was most potent for 24, 48 and 72 h treatment of cancer cells but it was not selective towards cancer over normal cells. The mechanistic studies of the cobalt(II) complex 1 involved apoptosis assay, cell cycle analysis, dichloro-dihydro-fluorescein diacetate assay, intracellular reactive oxygen species assay and proteasome inhibition assay. Complex 1 induced low apoptosis, generated low level of ROS and did not inhibit proteasome in normal cells. The study of the DNA binding and nucleolytic properties of complexes 1-3 in the absence or presence of HO or sodium ascorbate revealed that only complex 1 was not nucleolytic.
钴（II）、铜（II）和锌（II）配合物的合成、表征及对乳腺癌细胞系 MCF-7 和 MDA-MB-231 的体外抗肿瘤活性研究
本文报道了 1,10-菲啰啉（phen）和麦芽酚（mal）的钴（II）、铜（II）和锌（II）配合物（分别为 1、2、3）的合成、表征及对乳腺癌细胞系 MCF-7 和 MDA-MB-231 的体外抗肿瘤活性研究。通过 FT-IR、元素分析、UV 光谱、摩尔电导率、对硝基-N,N-二甲基苯胺（p-nitrosodimethylaniline）测定和质谱等方法对配合物进行了表征。锌（II）类似物的单晶 X 射线结构表明其具有明显较短的顶点氯键的正方形金字塔结构。通过（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法和形态学研究，评估了这些配合物对乳腺癌细胞系 MCF-7 和 MDA-MB-231 及正常细胞系 MCF-10A 的抗癌活性。结果表明，配合物 2 对癌细胞的 24、48 和 72 h 处理最为有效，但对癌细胞与正常细胞的选择性不高。钴（II）配合物 1 的机制研究包括凋亡测定、细胞周期分析、二氯二氢荧光素二乙酸酯测定、细胞内活性氧（ROS）测定和蛋白酶体抑制测定。结果表明，配合物 1 在正常细胞中诱导低凋亡、产生低水平的 ROS，并且不抑制蛋白酶体。在无 HO 或抗坏血酸钠存在或存在的情况下，研究了配合物 1-3 的 DNA 结合和核酸酶性质，结果表明只有配合物 1 不是核酸酶。
