Hotze Anna C G, Caspers Sabrine E, de Vos Dick, Kooijman Huub, Spek Anthony L, Flamigni Anna, Bacac Marina, Sava Gianni, Haasnoot Jaap G, Reedijk Jan
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands.
J Biol Inorg Chem. 2004 Apr;9(3):354-64. doi: 10.1007/s00775-004-0531-6. Epub 2004 Mar 19.
The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes.
二氯双（2-苯基偶氮吡啶）钌（II）配合物[Ru(azpy)(2)Cl(2)]因其潜在的抗癌活性而再次受到研究。合成了三种最常见的异构体α-、β-和γ-[RuL(2)Cl(2)]，其中L = 邻甲苯基偶氮吡啶（tazpy）和4-甲基-2-苯基偶氮吡啶（mazpy）（α表示配位的Cl、N（吡啶）和Nazo原子处于相互顺式、反式、顺式位置，β表示配位的Cl、N（吡啶）和Nazo原子处于相互顺式、顺式、顺式位置，γ表示配位的Cl、N（吡啶）和Nazo原子处于相互反式、顺式、顺式位置），并通过核磁共振光谱进行了表征。通过X射线衍射分析确定了γ-[Ru(tazpy)(2)Cl(2)]和α-[Ru(mazpy)(2)Cl(2)]的分子结构。在一系列人类肿瘤细胞系（MCF-7、EVSA-T、WIDR、IGROV、M19、A498和H266）中测定了几何异构体[Ru(tazpy)(2)Cl(2)]和[Ru(mazpy)(2)Cl(2)]配合物与母体[Ru(azpy)(2)Cl(2)]配合物的IC(50)值。这些数据明确显示了所有配合物的以下趋势：α异构体显示出非常高的细胞毒性，而β异构体的细胞毒性则低10倍。[Ru(tazpy)(2)Cl(2)]和[Ru(mazpy)(2)Cl(2)]的γ异构体显示出非常高的细胞毒性，与母体化合物[Ru(azpy)(2)Cl(2)]的γ异构体和α异构体相当。这些生物学数据对于更好地理解异构体[RuL(2)Cl(2)]配合物的构效关系至关重要。
