紫苏醇芳基钌配合物的合成及抗肿瘤性能

Synthesis and Antitumor Properties of Ruthenium-Arene Complexes Based on Natural Product Perillol

紫苏醇作为既有癌症预防又有癌症治疗作用的少数几种天然产物之一,曾作为临床药物用于癌症的治疗。但是紫苏醇通过口服给药生物利用度低、给药剂量大,因而限制了它的临床应用。我们将紫苏醇进行化学修饰,作为配体引入到芳基金属配合物中,合成了一种新型芳基钌配合物Ru-L,并利用核磁共振氢谱、碳谱、电喷雾质谱及元素分析对其进行了基础表征。配合物Ru-L对肿瘤细胞A2780、A2780/DDP及MCF-7都表现出较高的细胞毒活性,而对正常细胞株毒性较小(IC50>200μmol·L^-1),表明紫苏醇芳基钌配合物可以克服紫苏醇给药量大和毒性大等缺陷。紫外可见及荧光光谱表明配合物具有较快的水解速率,可通过嵌入作用与CT-DNA结合,并通过静态猝灭与BSA/HSA相互作用。流式细胞术也揭示配合物将肿瘤细胞周期阻滞在G0/G1期,从而导致了肿瘤细胞的凋亡。以上结果表明,基于紫苏醇的芳基钌配合物Ru-L克服了紫苏醇的高剂量、高毒性等缺点。

As one of the few natural products that is useful both in the prevention and treatment of cancers,perillol has been used as a clinical drug for the treatment of cancer.However,perillol has low bioavailability and large dos-age by oral administration,which limits its clinical application.In this work,perillol was chemically modified and introduced into the metal-arene complex as a ligand,thus a novel ruthenium-arene complex Ru-L was synthesized and characterized by NMR,ESI-MS and elemental analysis.The complex exhibited high cytotoxic activity against several tumor cells A2780,A2780/DDP and MCF-7,while it was none toxic to the normal cell lines(IC50>200μmol·L^-1).Absorbance and fluorescence spectra suggested that the complex had a fast hydrolysis rate,could bind to CT-DNA with a high affinity through intercalation mode and interact with BSA/HSA by static quenching.Flow cytome-try also revealed that the complex induced tumor cell cycle arrest in the G0/G1 phase,which led to apoptosis of tu-mor cells.The above results indicate that the ruthenium-arene complex Ru-L based on perillol can overcome the disadvantages of perillyl alcohol,such as its high doses and severe toxicity.