Evaluation of the Toxicity of Two Electron-Deficient Half-Sandwich Complexes against Human Lymphocytes from Healthy Individuals
Evaluation of the Toxicity of Two Electron-Deficient Half-Sandwich Complexes against Human Lymphocytes from Healthy Individuals
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DOI：
10.1002/cmdc.202000672
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发表时间：
2020-11-24
期刊：
影响因子：
3.4
通讯作者：
Barry, Nicolas P. E.
中科院分区：
文献类型：
--
作者：
Habas, Khaled;Soldevila-Barreda, Joan J.;Barry, Nicolas P. E.
缺电子半夹心配合物是一类研究不足的有机金属化合物，具有潜在的金属药物候选物。本文研究了两种16电子有机钌配合物[（p-cym）Ru（benzene-1，2-dithiolato）]（1）和[（p-cym）Ru（maleonitriledithiolate）]（2）对健康人非永生化淋巴细胞活力的影响。还通过使用彗星和微核阻断试验研究了1和2在淋巴细胞中的遗传毒性作用。对一组参与细胞凋亡和DNA损伤修复反应的基因进行了基因表达研究。结果表明，这两种16电子络合物对健康人淋巴细胞的细胞活力没有显著影响。然而，DNA损伤的增加是由两种化合物诱导的，可能是通过氧化应激产生。
Electron-deficient half-sandwich complexes are a class of under-studied organometallics with demonstrated potential as metallodrug candidates. This study investigates the effect of two 16-electron organoruthenium complexes ([(p-cym)Ru(benzene-1,2-dithiolato)] (1) and [(p-cym)Ru(maleonitriledithiolate)] (2)) on the cell viability of non-immortalised human lymphocytes from healthy individuals. The genotoxic effects of 1 and 2 in lymphocytes are also investigated by using the Comet and cytokinesis-block micronucleus assays. Gene expression studies were carried out on a panel of genes involved in apoptosis and the DNA damage-repair response. Results show that the two 16-electron complexes do not have significant effect on the cell viability of human lymphocytes from healthy individuals. However, an increase in DNA damage is induced by both compounds, presumably through oxidative stress production.