Poletaeva Darya A, Soldatova Yuliya V, Smolina Anastasiya V, Savushkin Maxim A, Klimanova Elena N, Sanina Nataliya A, Faingold Irina I
Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue, 1142432 Chernogolovka, Russia.
Faculty of Fundamental Physical and Chemical Engineering, Moscow State University, 1142432 Moscow, Russia.
Membranes (Basel). 2022 Nov 2;12(11):1088. doi: 10.3390/membranes12111088.
This paper shows the biological effects of cationic binuclear tetranitrosyl iron complex with penicillamine ligands (TNIC-PA). Interaction with a model membrane was assessed using a fluorescent probes technique. Antioxidant activity was studied using a thiobarbituric acid reactive species assay (TBARS) and a chemiluminescence assay. The catalytic activity of monoamine oxidase (MAO) was determined by measuring liberation of ammonia. Antiglycation activity was determined fluometrically by thermal glycation of albumine by D-glucose. The higher values of Stern-Volmer constants (K) obtained for the pyrene located in hydrophobic regions (3.9 × 10 M) compared to K obtained for eosin Y located in the polar headgroup region (0.9 × 10 M) confirms that TNIC-PA molecules prefer to be located in the hydrophobic acyl chain region, close to the glycerol group of lipid molecules. TNIC-PA effectively inhibited the process of spontaneous lipid peroxidation, due to additive contributions from releasing NO and penicillamine ligand (IC50 = 21.4 µM) and quenched luminol chemiluminescence (IC50 = 3.6 μM). High activity of TNIC-PA in both tests allows us to assume a significant role of its radical-scavenging activity in the realization of antioxidant activity. It was shown that TNIC-PA (50-1000 μM) selectively inhibits the membrane-bound enzyme MAO-A, a major source of ROS in the heart. In addition, TNIC-PA is an effective inhibitor of non-enzymatic protein glycation. Thus, the evaluated biological effects of TNIC-PA open up the possibility of its practical application in chemotherapy for socially significant diseases, especially cardiovascular diseases.
本文展示了含青霉胺配体的阳离子双核四亚硝基铁配合物（TNIC-PA）的生物学效应。使用荧光探针技术评估其与模型膜的相互作用。采用硫代巴比妥酸反应性物质测定法（TBARS）和化学发光测定法研究抗氧化活性。通过测量氨的释放来测定单胺氧化酶（MAO）的催化活性。通过D-葡萄糖对白蛋白进行热糖化反应，采用荧光法测定抗糖基化活性。与位于极性头部基团区域的曙红Y所获得的斯特恩-沃尔默常数（K）值（0.9×10 M）相比，位于疏水区域的芘所获得的K值更高（3.9×10 M），这证实TNIC-PA分子更倾向于位于疏水酰基链区域，靠近脂质分子的甘油基团。由于释放一氧化氮和青霉胺配体的累加作用，TNIC-PA有效抑制了自发脂质过氧化过程（IC50 = 21.4 μM），并淬灭了鲁米诺化学发光（IC50 = 3.6 μM）。在这两种测试中TNIC-PA的高活性使我们能够假定其自由基清除活性在抗氧化活性的实现中起重要作用。结果表明，TNIC-PA（50 - 1000 μM）选择性抑制膜结合酶MAO-A，MAO-A是心脏中活性氧的主要来源。此外，TNIC-PA是一种有效的非酶蛋白糖基化抑制剂。因此，TNIC-PA所评估的生物学效应为其在治疗具有社会意义的疾病，尤其是心血管疾病的化疗中的实际应用开辟了可能性。
