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Anticancer activity of 4'-phenyl-2,2':6',2″-terpyridines - behind the metal complexation.
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.ejmech.2020.112039 Katarzyna Malarz 1 , Dawid Zych 2 , Michał Kuczak 3 , Robert Musioł 2 , Anna Mrozek-Wilczkiewicz 1
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.ejmech.2020.112039 Katarzyna Malarz 1 , Dawid Zych 2 , Michał Kuczak 3 , Robert Musioł 2 , Anna Mrozek-Wilczkiewicz 1
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Terpyridine complexes are known for their broad biological activities, of which their anticancer potency is the most extensively studied. Strikingly, free ligand activity has rarely been described in the literature. In this study, a lipophilic derivative of terpyridine 4'-(1-decyl-2,3-triazol-4-yl)phenyl-2,2':6',2″-terpyridine (L) and its complexes were investigated to determine their mechanism of anticancer activity. Our results show that a free ligand expresses the same level of activity on a panel of cancer cells with a low toxicity towards normal fibroblasts as complexes with Cd, Zn or Cu. Breast cancer (MCF-7 cell line) was the most vulnerable for the tested compounds with the IC50 values in the nanomolar range (IC50 = 40 nM for L.) The addition of Cu(II) ions increased its activity even further, thus suggesting that ligand exchange and ROS production are the main components of its activity. A cell cycle analysis indicated its inhibition at the G0/G1 phase and the subsequent apoptosis as the cell death mode. A detailed analysis of the protein level that was involved in the aforementioned processes confirmed previous results. Furthermore, the reactive oxygen species generation and DNA intercalation confirmed its cleaving activity.
中文翻译：
金属络合后的4'-苯基-2,2'：6'，2''-叔吡啶的抗癌活性。
特吡啶吡啶复合物以其广泛的生物学活性而著称，其中其抗癌效力得到了最广泛的研究。引人注目的是，文献中很少描述自由配体的活性。在这项研究中，对三联吡啶4'-（1-癸基-2,3-三唑-4-基）苯基-2,2'：6'，2''-联吡啶（L）的亲脂性衍生物进行了研究，确定其抗癌活性的机制。我们的结果表明，游离配体在一组癌细胞中表达的活性水平与Cd，Zn或Cu的复合物相同，且对正常成纤维细胞的毒性低。乳腺癌（MCF-7细胞系）是最易受测试的化合物，其IC50值在纳摩尔范围内（L的IC50 = 40 nM。）添加Cu（II）离子可进一步提高其活性，因此表明配体交换和活性氧的产生是其活性的主要组成部分。细胞周期分析表明其在G0 / G1期的抑制作用和随后的细胞凋亡作为细胞死亡模式。对上述过程中涉及的蛋白质水平的详细分析证实了先前的结果。此外，活性氧的产生和DNA插入证实了其裂解活性。
更新日期：2020-01-09
中文翻译：
金属络合后的4'-苯基-2,2'：6'，2''-叔吡啶的抗癌活性。
特吡啶吡啶复合物以其广泛的生物学活性而著称，其中其抗癌效力得到了最广泛的研究。引人注目的是，文献中很少描述自由配体的活性。在这项研究中，对三联吡啶4'-（1-癸基-2,3-三唑-4-基）苯基-2,2'：6'，2''-联吡啶（L）的亲脂性衍生物进行了研究，确定其抗癌活性的机制。我们的结果表明，游离配体在一组癌细胞中表达的活性水平与Cd，Zn或Cu的复合物相同，且对正常成纤维细胞的毒性低。乳腺癌（MCF-7细胞系）是最易受测试的化合物，其IC50值在纳摩尔范围内（L的IC50 = 40 nM。）添加Cu（II）离子可进一步提高其活性，因此表明配体交换和活性氧的产生是其活性的主要组成部分。细胞周期分析表明其在G0 / G1期的抑制作用和随后的细胞凋亡作为细胞死亡模式。对上述过程中涉及的蛋白质水平的详细分析证实了先前的结果。此外，活性氧的产生和DNA插入证实了其裂解活性。
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