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二茂铁基和六羰基二钴色酮——诱导氧化应激并使人类癌细胞停滞于G2/M期的新型有机金属化合物。

Ferrocenyl and dicobalt hexacarbonyl chromones--new organometallics inducing oxidative stress and arresting human cancer cells in G2/M phase.

作者信息

Kowalski Konrad, Hikisz Paweł, Szczupak Łukasz, Therrien Bruno, Koceva-Chyła Aneta

机构信息

Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.

Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.

出版信息

Eur J Med Chem. 2014 Jun 23;81:289-300. doi: 10.1016/j.ejmech.2014.05.023. Epub 2014 May 9.

Abstract

The straightforward syntheses of four new ferrocenyl and dicobalt hexacarbonyl chromones are presented. The redox behavior of the novel metallo-chromones has been examined by cyclic voltammetry (CV), revealing a reversible behavior of the ferrocenyl groups, while the dicobalt hexacarbonyl derivatives show irreversible oxidation. The anticancer activity of the products has been evaluated against hepatocellular carcinoma (Hep G2), ER+ (MCF-7) and ER- (MDA-MB-231) breast adenocarcinoma, and leukemic (CCRF-CEM) human cancer cell lines. The mechanism of action for the most active complexes has been investigated and it seems to involve oxidative stress and apoptosis induction. Moreover, the results show that the investigated metallo-chromones generate damage to DNA and arrest the cell cycle in G2/M phase.

摘要

本文介绍了四种新型二茂铁基和六羰基二钴色酮的直接合成方法。通过循环伏安法(CV)研究了新型金属色酮的氧化还原行为,结果表明二茂铁基团具有可逆行为,而六羰基二钴衍生物则表现出不可逆氧化。评估了这些产物对肝癌(Hep G2)、雌激素受体阳性(MCF-7)和雌激素受体阴性(MDA-MB-231)乳腺腺癌以及白血病(CCRF-CEM)人癌细胞系的抗癌活性。对活性最高的配合物的作用机制进行了研究,似乎涉及氧化应激和凋亡诱导。此外,结果表明所研究的金属色酮会对DNA造成损伤并使细胞周期停滞在G2/M期。

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