Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria.
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Arch Pharm (Weinheim). 2020 Jul;353(7):e2000039. doi: 10.1002/ardp.202000039. Epub 2020 Apr 24.
In this study, a Pt(IV) complex with 3'-methyl-4-thio-1H-tetrahydropyranspiro-5'-hydantoin (complex 1) was synthesized. The structure was determined via elemental analyses, infrared, H, and C nuclear magnetic resonance techniques. Density functional theory calculations were applied to optimize the molecular geometry and to calculate structural parameters and vibrational frequencies. The cytotoxicity of the newly synthesized complex 1 was assessed against K-562 and REH cells and compared with the cytotoxic effects of the ligand (L) and its Pd(IV) complex (complex 2). Complex 1 exhibited a better cytotoxic activity (IC = 76.9 µM against K-562 and 15.6 µM against REH cells) than L and complex 2, which was closer to the cytotoxic effect of cisplatin (IC = 36.9 μM and 1.07 μM against K-562 and REH cells, respectively), as compared with the ligand and complex 2. L and its complexes 1 and 2 were evaluated for inhibitory activity against xanthine oxidase (XO) in vitro, as compared with allopurinol (IC = 1.70 μM). Complex 1 was shown as a potent XO inhibitor, with an IC value of 19.33 μM, and the binding mode with the enzyme was predicted by molecular docking. Its inhibitory activity against XO is a potential advantage that might result in improved profile and anticancer activity.
在这项研究中，合成了一种带有 3'-甲基-4-硫-1H-四氢吡喃螺-5'-海因（配合物 1）的 Pt(IV) 配合物。通过元素分析、红外、 H 和 C 核磁共振技术确定了其结构。应用密度泛函理论计算对分子几何形状进行了优化，并计算了结构参数和振动频率。评估了新合成的配合物 1 对 K-562 和 REH 细胞的细胞毒性，并将其与配体 (L) 和其 Pd(IV) 配合物 (配合物 2) 的细胞毒性进行了比较。配合物 1 表现出更好的细胞毒性活性（对 K-562 的 IC = 76.9 µM，对 REH 细胞的 IC = 15.6 µM），优于配体和配合物 2，与顺铂的细胞毒性（对 K-562 的 IC = 36.9 μM，对 REH 细胞的 IC = 1.07 μM）更接近，与配体和配合物 2 相比。与别嘌呤醇（IC = 1.70 μM）相比，评估了 L 及其配合物 1 和 2 对黄嘌呤氧化酶 (XO) 的体外抑制活性。配合物 1 表现出很强的 XO 抑制活性，IC 值为 19.33 μM，并通过分子对接预测了其与酶的结合模式。其对 XO 的抑制活性可能是改善其特性和抗癌活性的潜在优势。
