N6-Benzyladenosine Derivatives as Novel N-Donor Ligands of Platinum(II) Dichlorido Complexes
作者:Pavel Štarha、Igor Popa、Zdeněk Trávníček、Ján Vančo
DOI:10.3390/molecules18066990
日期:——
The platinum(II) complexes trans-[PtCl2(Ln)2]∙xSolv 1–13 (Solv = H2O or CH3OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; Ln stands for N6-(2-methoxybenzyl)adenosine (L1, involved in complex 1), N6-(4-methoxy-benzyl)adenosine (L2, 2), N6-(2-chlorobenzyl)adenosine (L3, 3), N6-(4-chlorobenzyl)-adenosine (L4, 4), N6-(2-hydroxybenzyl)adenosine (L5, 5), N6-(3-hydroxybenzyl)-adenosine (L6, 6), N6-(2-hydroxy-3-methoxybenzyl)adenosine (L7, 7), N6-(4-fluoro-benzyl)adenosine (L8, 8), N6-(4-methylbenzyl)adenosine (L9, 9), 2-chloro-N6-(3-hydroxy-benzyl)adenosine (L10, 10), 2-chloro-N6-(4-hydroxybenzyl)adenosine (L11, 11), 2-chloro-N6-(2-hydroxy-3-methoxybenzyl)adenosine (L12, 12) and 2-chloro-N6-(2-hydroxy-5-methylbenzyl)adenosine (L13, 13). The compounds were characterized by elemental analysis, mass spectrometry, IR and multinuclear (1H-, 13C-, 195Pt- and 15N-) and two-dimensional NMR spectroscopy, which proved the N7-coordination mode of the appropriate N6-benzyladenosine derivative and trans-geometry of the title complexes. The complexes 1–13 were found to be non-toxic in vitro against two selected human cancer cell lines (HOS and MCF7; with IC50 > 50.0 µM). However, they were found (by ESI-MS study) to be able to interact with the physiological levels of the sulfur-containing biogenic biomolecule L-methionine by a relatively simple 1:1 exchange mechanism (one Ln molecule was replaced by one L-methionine molecule), thus forming a mixed-nitrogen/sulfur-ligand dichlorido-platinum(II) coordination species.
合成了铂(II)复合物trans-[PtCl2(Ln)2]∙xSolv 1–13(Solv = H2O或CH3OH),这些复合物涉及以N6-苄基腺苷为基础的N供体配体;Ln代表N6-(2-甲氧基苄基)腺苷(L1,复合物1中涉及),N6-(4-甲氧基苄基)腺苷(L2,复合物2),N6-(2-氯苄基)腺苷(L3,复合物3),N6-(4-氯苄基)腺苷(L4,复合物4),N6-(2-羟基苄基)腺苷(L5,复合物5),N6-(3-羟基苄基)腺苷(L6,复合物6),N6-(2-羟基-3-甲氧基苄基)腺苷(L7,复合物7),N6-(4-氟苄基)腺苷(L8,复合物8),N6-(4-甲基苄基)腺苷(L9,复合物9),2-氯-N6-(3-羟基苄基)腺苷(L10,复合物10),2-氯-N6-(4-羟基苄基)腺苷(L11,复合物11),2-氯-N6-(2-羟基-3-甲氧基苄基)腺苷(L12,复合物12)和2-氯-N6-(2-羟基-5-甲基苄基)腺苷(L13,复合物13)。通过元素分析、质谱、红外光谱以及多核(1H、13C、195Pt和15N)和二维核磁共振谱对这些化合物进行了表征,证明了适当的N6-苄基腺苷衍生物的N7配位模式和标题复合物的反式几何结构。复合物1–13在体外对选定的人癌细胞系(HOS和MCF7;IC50 > 50.0 µM)被发现无毒。然而,通过ESI-MS研究发现,它们能够通过相对简单的1:1置换机制(一个Ln分子被一个L-甲硫氨酸分子替换)与生理水平的含硫生物源生物分子L-甲硫氨酸相互作用,从而形成混合氮/硫配体的二氯铂(II)配位物。