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Effect of the hydroxamate group in the antitumoral activity and toxicity toward normal cells of new copper(II) complexes
Biometals ( IF 3.5 ) Pub Date : 2021-02-09 , DOI: 10.1007/s10534-020-00275-9
Nathália F B Azeredo 1 , Franz V Borges 2 , Marcelo S Mathias 1 , Jackson A L C Resende 3 , Roberto W A Franco 4 , Milton M Kanashiro 5 , Adolfo Horn 6 , Christiane Fernandes 6
Affiliation  

The synthesis, physico–chemical characterization and cytotoxicity of four copper(II) coordination complexes, i.e. [Cu(HBPA)Cl2] (1), [Cu(BHA)2] (2), [Cu(HBPA)(BHA)Cl] CH3OH (3) and [Cu(HBPA)2]Cl2·4H2O (4), are reported. HBPA is the tridentate ligand N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)amine and HBHA is the benzohydroxamic acid. The reaction between the HBHA and CuCl2.2H2O has resulted in the new complex (2) and the reaction between complex (1) and HBHA has resulted in the new complex (3). X-ray diffraction studies for complex (3) indicated the effective coordination of HBHA as BHA. Their cytotoxicity was evaluated against three human tumoral cell lines (Colo-205, NCI-H460 and U937) and PBMC (peripheral blood mononuclear cells), using the MTT cytotoxic assay. The results toward PBMC reveal that the new copper(II) complex (2) presents lower toxicity toward normal cells. Furthermore, complex (2) presents IC50 values lower than cisplatin toward NCI-H460 and the best selectivity index obtained towards NCI-H460 (SI = 2.2) and U937 cell lines (SI = 2.0), as a result of the presence of two molecules of HBHA in its structure. Complex (3) presents IC50 values lower than cisplatin toward NCI-H460, Colo-205 and comparable to cisplatin toward U937. The evaluation of the cell death type promoted by complexes (2) and (4) was investigated toward NCI-H460 revealing better results than the standard drug cisplatin, according to the Annexin V and propidium iodide (PI) labeling experiment. Based on the studies here performed, HBHA seems to be related to lower toxicity toward PBMC and HBPA is improving directly the cytotoxity.



中文翻译:

异羟肟酸酯基团对新铜(II)配合物的抗肿瘤活性和对正常细胞毒性的影响

四种铜 (II) 配位配合物的合成、理化表征和细胞毒性,即 [Cu(HBPA)Cl 2 ] (1) , [Cu(BHA) 2 ] (2) , [Cu(HBPA)(BHA)报道了Cl] CH 3 OH (3)和[Cu(HBPA) 2 ]Cl 2 ·4H 2 O (4)。HBPA 是三齿配体 N-(2-羟基苄基)-N-(2-吡啶基甲基)胺,HBHA 是苯异羟肟酸。所述的HBHA和氯化亚铜之间反应2 ·2H 2 O具有导致新的复杂(2)和复杂的反应(1)HBHA 产生了新的复合体(3)。复合物(3) 的X 射线衍射研究表明 HBHA 作为 BHA -的有效配位。使用 MTT 细胞毒性试验评估了它们对三种人类肿瘤细胞系(Colo-205、NCI-H460 和 U937)和 PBMC(外周血单核细胞)的细胞毒性。PBMC 的结果表明,新的铜 (II) 复合物(2)对正常细胞的毒性较低。此外,复合体(2)呈现 IC 50由于其结构中存在两个 HBHA 分子,因此对 NCI-H460 的值低于顺铂,而对 NCI-H460 (SI = 2.2) 和 U937 细胞系 (SI = 2.0) 的选择性指数最佳。复合物(3)对 NCI-H460、Colo-205 的IC 50值低于顺铂,而对 U937 的IC 50值与顺铂相当。根据膜联蛋白 V 和碘化丙啶 (PI) 标记实验,针对 NCI-H460 对复合物(2)(4)促进的细胞死亡类型的评估显示出比标准药物顺铂更好的结果。根据此处进行的研究,HBHA 似乎与对 PBMC 的较低毒性有关,而 HBPA 直接提高了细胞毒性。

更新日期:2021-02-09
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