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Evaluation of cobalt(III) complexes as potential hypoxia-responsive carriers of esculetin.
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2020-08-08 , DOI: 10.1016/j.jinorgbio.2020.111211
Marcos V Palmeira-Mello 1 , Ana B Caballero 2 , Juliana Martins Ribeiro 3 , Elaine Maria de Souza-Fagundes 3 , Patrick Gamez 4 , Mauricio Lanznaster 5
Affiliation  

Differentiation between hypoxic and normoxic tissues have been exploited for the development of selective chemotherapeutic agents. In this context, cobalt(III)-based coordination compounds have been designed and investigated as prospective hypoxia-responsive drug delivery systems. Three cobalt(III) complexes, namely [CoIII(esc)(py2en)]ClO4·(CH3OH)2 (1) [CoIII(esc)(TPA)]ClO4·3H2O (2) and [CoIII(bipy)2(esc)]ClO4·2.5H2O (3) (py2en = N,N′-bis(pyridin-2-ylmethyl)ethylenediamine, TPA = tris(2-pyridylmethyl)amine, bipy = 2,2′-bipyridine and esc = 6,7-dihydroxycoumarin or esculetin), were prepared and investigated as potential carriers of esculetin. The spectroscopic and electrochemical properties of 13 were investigated and compared. Reactions of the complexes with biologically relevant reducing agents, viz. ascorbic acid, cysteine and glutathione, were monitored spectroscopically for 24 h, in pH 6.2 and 7.4 PBS phosphate buffer saline (PBS) solutions at 37 °C, under air, argon and dioxygen atmospheres. Dissociation of esculetin was observed upon Co3+/Co2+ reduction preferably under hypoxic conditions, with more effective conversion rates for 3 > 2 > 1. These results illustrate the importance to modulate the Co3+/Co2+ redox potential through the donor-acceptor properties of the ancillary ligands. Complex 3 is cytotoxic against HCT-116 but not against HT-29 and HEK-293 cells. In addition, DNA-binding studies indicate that interactions of 1 and 3 with the biomolecule are electrostatic.



中文翻译:

钴(III)复合物作为七叶皂苷的潜在低氧反应性载体的评估。

缺氧和常氧组织之间的分化已被用于开发选择性化学治疗剂。在这种情况下,已经设计并研究了基于钴(III)的配位化合物,并将其作为预期的低氧反应性药物递送系统。三种钴(III)配合物,即[Co III(esc)(py 2 en)] ClO 4 ·(CH 3 OH)21)[Co III(esc)(TPA)] ClO 4 ·3H 2 O(2)和[Co III(bipy)2(esc)] ClO 4 ·2.5H 2 O(3)(py 2en =  NN'-双(吡啶-2-基甲基)乙二胺,TPA =三(2-吡啶基甲基)胺,bipy = 2,2'-联吡啶和esc = 6,7-二羟基香豆素或七叶亭)。被调查为七叶皂苷的潜在载体。的光谱和电化学性质1 - 3进行了研究和比较。络合物与生物学相关的还原剂的反应,即。在37°C的空气,氩气和双氧气氛下,在pH 6.2和7.4 PBS磷酸盐缓冲盐水(PBS)溶液中,以光谱法监测抗坏血酸,半胱氨酸和谷胱甘肽24小时。在Co 3+ / Co 2+时观察到七叶皂苷的解离还原最好在缺氧条件下进行,且3  >  2  >  1的转化率更高。这些结果说明了通过辅助配体的供体-受体性质调节Co 3+ / Co 2+氧化还原电势的重要性。复合物3对HCT-116具有细胞毒性,但对HT-29和HEK-293细胞不具有细胞毒性。另外,DNA结合研究表明13与生物分子的相互作用是静电的。

更新日期:2020-08-14
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