曹亚萍,易芩兰,刘洪梅,李海霞,左建丽,袁泽利

    (遵义医学院 药学院，贵州 遵义 563099)

    基础医学研究

    氨基酸席夫碱氧钒(IV)配合物的合成、晶体结构及其抗肿瘤活性

    曹亚萍,易芩兰,刘洪梅,李海霞,左建丽,袁泽利

    (遵义医学院 药学院，贵州 遵义563099)

    [摘要]目的 开发具有新生物活性的非铂系前药。方法 采用一锅合成法合成3个新的氨基酸席夫碱和1,10-邻菲罗啉(IV)配合物[VO(o-van-Naph-L-Ana)(Phen)](o-van-Naph-L-Ana为邻香草醛与 3-(1-萘基)-L-丙氨酸缩合成的席夫碱，Phen为1,10-邻菲罗啉)(1)、[VO(Hynaph-L-Tyr)(Phen)] (Hynaph-L-Tyr为2-羟基-1-萘甲醛与L-色氨酸缩合成的席夫碱, Phen=1,10-邻菲罗啉)(2)和[VO(o-van-L-Trp)(Phen)](o-van-L-Trp为邻香草醛与L-色氨酸缩合成的席夫碱, Phen=1,10-邻菲罗啉)(3)，利用高分辨质谱、FT-IR谱及摩尔电导进行了表征研究，并通过X 射线单晶衍射测定了其晶体结构。用MTT法测定目标配合物1、2和3对A549(人肺腺癌细胞)和 HepG2(人源肝癌细胞)的体外抗肿瘤活性。结果 成功合成了3个新的钒氧氨基酸席夫碱配合物。3个目标配合物的体外抗肿瘤实验结果表明：配合物2和3对两种受试细胞株均表现出一定的细胞毒性，2和3对A549的IC50分别为58.88和53.08 μmol/L，对HepG2的IC50分别为：83.95和44.74 μmol/L。结论 探寻了一种具有反应条件温和、后处理简单的一锅合成方法。合成得到的3个目标配合物中，化合物2和3对A549和HepG2细胞具有中等活性。

    [关键词]氨基酸；席夫碱；氧钒(IV)配合物；晶体结构；抗肿瘤活性

    In the past few decades, transition metal complexes have been extensively studied as anticancer agents following the discovery ofcis-platin as an effective chemotherapeutic drug[1-3]. Vanadium is an nessential trace metal in life processes, and it occupies an important position inmetallo -pharmaceuticals due to its pharmacological functions. Meanwhile, in many transition metal materials, oxovanadium salts are less expensive than K2PtCl4, RuCl3, or VCl3materials and make for more suitable vanadium-based drug research and development for inexpensive drugs. On the other hand, current research suggests that transformed cells maintain an abnormal redox homeostasis that helps them to obtain optimal genetic instability, which is conducive to cancer progression[4-5]. Vanadium’s intrinsic redox activity can generate reactive oxygen species (ROS). This enhanced level of ROS can disorganize the redox homeostasis in neoplastic cells and impart redox stress to the cell apoptosis either by cleaving DNA or by promoting mitochondrial membrane permeabilisation[6]. Moreover, a growing body of evidence reveals that vanadium complexes can act as potent anticancer agents[7-8]. Although inorganic vanadium salts have relatively high toxicity and poor biological activity, some research has shown that the complexation of vanadium with organic ligands minimizes adverse effects and usually aggrandizes the important benefits. Therefore, it is important to synthesize novel oxovanadium complexes to investigate their medical application. ......