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氧化钒(V)缬氨酸席夫碱配位化合物的合成、表征及体外胰岛素模拟活性评价

Synthesis, Characterization, and In Vitro Insulin-Mimetic Activity Evaluation of Valine Schiff Base Coordination Compounds of Oxidovanadium(V).

作者信息

Turtoi Mihaela, Anghelache Maria, Patrascu Andrei A, Maxim Catalin, Manduteanu Ileana, Calin Manuela, Popescu Delia-Laura

机构信息

Medical and Pharmaceutical Bionanotechnologies Laboratory, Institute of Cellular Biology and Pathology Nicolae Simionescu of the Romanian Academy, 8 B.P. Hasdeu, 050568-Bucharest, Romania.

Department of Inorganic Chemistry, Faculty of Chemistry, University of Bucharest, 23 Dumbrava Roşie, 020464-Bucharest, Romania.

出版信息

Biomedicines. 2021 May 17;9(5):562. doi: 10.3390/biomedicines9050562.

Abstract

Type 2 diabetes became an alarming global health issue since the existing drugs do not prevent its progression. Herein, we aimed to synthesize and characterize a family of oxidovanadium(V) complexes with Schiff base ligands derived from L-/D-valine (val) and salicylaldehyde (sal) or -vanillin (van) as insulin-mimetic agents and to assess their potential anti-diabetic properties. Two new oxidovanadium(V) complexes, [{VO(R-salval)(HO)}(μ-O){VO(R-salval)}] and [{VO(R-vanval)(CHOH)}(μ-O)], and their S-enantiomers were synthesized and characterized. The compounds exhibit optical activity as shown by crystallographic and spectroscopic data. The stability, the capacity to bind bovine serum albumin (BSA), the cytotoxicity against human hepatoma cell line, as well as the potential anti-diabetic activity of the four compounds are investigated. The synthesized compounds are stable for up to three hours in physiological conditions and exhibit a high capacity of binding to BSA. Furthermore, the synthesized compounds display cytocompatibility at biologically relevant concentrations, exert anti-diabetic potential and insulin-mimetic activities by inhibiting the α-amylase and protein tyrosine phosphatase activity, and a long-term increase of insulin receptor phosphorylation compared to the insulin hormone. Thus, the in vitro anti-diabetic potential and insulin-mimetic properties of the newly synthesized oxidovanadium(V) compounds, correlated with their cytocompatibility, make them promising candidates for further investigation as anti-diabetic drugs.

摘要

由于现有药物无法阻止2型糖尿病的发展,它已成为一个令人担忧的全球健康问题。在此,我们旨在合成并表征一系列以L-/D-缬氨酸(val)和水杨醛(sal)或香草醛(van)衍生的席夫碱配体作为胰岛素模拟剂的氧化钒(V)配合物,并评估它们潜在的抗糖尿病特性。合成并表征了两种新的氧化钒(V)配合物,[{VO(R-salval)(HO)}(μ-O){VO(R-salval)}]和[{VO(R-vanval)(CHOH)}(μ-O)]及其S-对映体。晶体学和光谱数据表明这些化合物具有光学活性。研究了这四种化合物的稳定性、结合牛血清白蛋白(BSA)的能力、对人肝癌细胞系的细胞毒性以及潜在的抗糖尿病活性。合成的化合物在生理条件下长达三小时保持稳定,并表现出与BSA的高结合能力。此外,合成的化合物在生物学相关浓度下表现出细胞相容性,通过抑制α-淀粉酶和蛋白酪氨酸磷酸酶活性发挥抗糖尿病潜力和胰岛素模拟活性,并且与胰岛素激素相比,能使胰岛素受体磷酸化长期增加。因此,新合成的氧化钒(V)化合物的体外抗糖尿病潜力和胰岛素模拟特性,与其细胞相容性相关,使其成为作为抗糖尿病药物进一步研究的有希望的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/8156053/22fd414380ca/biomedicines-09-00562-g001.jpg

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