New water soluble, enantiopure arene ruthenium compound S_RuS_N-(1R,4S)-[(η⁶-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described R_RuR_N-(1S,4R)-[(η⁶-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC₅₀ values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.

新的水溶性，对映体纯芳烃钌化合物小号_孺小号_ñ - （1 - [R，4小号） - [（η ⁶ - p -cymene）的Ru {ĸNH（Bn），对ĸNOH} CL]氯（BN =苄基，1A '）已经合成。与先前描述的沿着新型化合物[R_孺ř _ñ - （1小号，4 - [R ）- [（η ⁶ - p -cymene）的Ru {ĸNH（Bn），对ĸNOH} CL]氯（1A）是通过旋光评价紫外和圆二色光谱。新型钌衍生物1a的结构通过单晶X射线晶体学测定'。两种对映异构体均已针对多种癌细胞系进行了体外测试：前列腺PC-3，肺A-549，胰腺MIA PaCa-2，结直肠癌HCT-116，白血病Jurkat和宫颈HeLa。两种对映异构体都是活性和通用的细胞毒性剂，其IC ₅₀值比在所评估的不同细胞系中顺铂的IC ₅₀值低2至12倍。在A-549和Jurkat细胞系中分析了由金属化合物诱导的细胞死亡机制。衍生物1a和1a′诱导了A-549细胞的凋亡细胞死亡，而在Jurkat细胞系中发现了剂量依赖性细胞死亡机制。已通过平衡透析，荧光共振能量转移（FRET）熔融测定法和粘度滴定法研究了化合物与DNA的相互作用，揭示了1a和1a '对双链DNA的中等结合亲和力。最后，已经评估了1a在裸鼠PC-3异种移植物的体内初步试验中的功效，从而有望将肿瘤生长抑制45％。肿瘤组织的分析还显示，PC-3细胞的侵袭性表型中的关键分子水平显着降低。