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槲皮素-苯丙氨酸 3d 过渡金属基 {Co(II)、Ni(II) 和 Cu(II)} 插层治疗剂:体外 DNA 和 BSA 相互作用研究及切割活性。

Quercetin-phenylalanine 3d-transition metal-based {Co(II), Ni(II) & Cu(II)} intercalative therapeutic agents: DNA & BSA interaction studies in vitro and cleavage activity.

机构信息

Department of Chemistry, Aligarh Muslim University, Aligarh 202002, UP, India.

Department of Chemistry, Aligarh Muslim University, Aligarh 202002, UP, India.

出版信息

Int J Biol Macromol. 2024 Jan;254(Pt 1):127521. doi: 10.1016/j.ijbiomac.2023.127521. Epub 2023 Oct 26.

Abstract

New Quercetin-phenylalanine metal-based therapeutic agents of the formulation [Qu(Phe)M(II).(HO)].NO where M(II) = Co(II) and Ni(II) and [Qu(Phe)Cu(II).(HO)] were synthesized and their structure was predicted by IR, UV-vis, EPR and ESI-MS spectroscopic techniques. The bio-molecular interaction studies of the Quercetin-phenylalanine complexes, 1-3 with ct-DNA and BSA were performed using a battery of complimentary biophysical techniques. The corroborative results of these experiments revealed strong binding propensity via electrostatic interactions probably through minor grove binding towards ct-DNA, therapeutic target. The binding affinity of Quercetin-phenylalanine complexes 1-3 was quantified by determining binding constants values, K, K, and the magnitude of binding propensity followed the order 3 > 1 > 2, implicating the preferential binding of Cu(II) complex 3 with ct-DNA. The cleavage studies were performed with complexes using gel electrophoretic mobility assay. The complexes 1-3 demonstrated efficient cleaving ability by the hydrolytic cleavage pathway involving hydroxyl (OH) radicals. BSA binding profile of Quercetin-phenylalanine metal therapeutics 1-3 was studied in order to understand the drug carrier potential of these compounds and found that complex 3 was capable of binding preferentially with BSA as compared to other complexes.

摘要

合成了 [Qu(Phe)M(II).(HO)].NO 形式的新型槲皮素-苯丙氨酸金属治疗剂,其中 M(II) = Co(II) 和 Ni(II),[Qu(Phe)Cu(II).(HO)],并通过 IR、UV-vis、EPR 和 ESI-MS 光谱技术预测了其结构。使用一系列互补的生物物理技术研究了 Quercetin-phenylalanine 配合物 1-3 与 ct-DNA 和 BSA 的生物分子相互作用。这些实验的协同结果表明,通过静电相互作用具有很强的结合倾向,可能通过小沟结合对治疗靶标 ct-DNA 具有亲和力。通过确定结合常数值 K、K 和结合倾向的大小定量了 Quercetin-phenylalanine 配合物 1-3 的结合亲和力,其顺序为 3>1>2,表明 Cu(II)配合物 3 与 ct-DNA 的优先结合。使用凝胶电泳迁移率测定法进行了配合物的切割研究。配合物 1-3 通过涉及羟基 (OH) 自由基的水解切割途径表现出有效的切割能力。为了了解这些化合物的药物载体潜力,研究了 Quercetin-phenylalanine 金属治疗剂 1-3 的 BSA 结合谱,发现与其他配合物相比,配合物 3 能够优先与 BSA 结合。

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