论文部分内容阅读
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Hep G2(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IC_50分别为58.88和53.08μmol/L,对Hep G2的IC50分别为:83.95和44.74μmol/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Hep G2细胞具有中等活性。
Objective To develop non-platinum-based prodrugs with novel biological activity. Methods Three new amino acid Schiff bases and 1,10-phenanthroline complexes [VO (o-van-Naph-L-Ana) Naph-L-Ana is a Schiff base formed by the condensation of o-vanillin with 3- (1-naphthyl) -L-alanine and Phen is 1,10-phenanthroline) Hynaph-L-Tyr) (Phen)] (Hynaph-L-Tyr is a Schiff base formed by the condensation of 2-hydroxy-1-naphthaldehyde with L-tryptophan, Phen = (O-van-L-Trp) is a Schiff base formed by the condensation of o-vanillin and L-tryptophan, Phen = 1, 10- Phenanthroline) (3). The characterization was carried out by high resolution mass spectrometry, FT-IR spectroscopy and molar conductance. The crystal structure was also determined by X-ray single crystal diffraction. In vitro antitumor activity of target complexes 1, 2 and 3 on A549 (human lung adenocarcinoma cells) and Hep G2 (human hepatoma cells) were determined by MTT assay. Results Three novel vanadyl amino acids Schiff base complexes were successfully synthesized. The antitumor activity of the three target complexes in vitro showed that the complexes 2 and 3 showed cytotoxicity to both cell lines, with IC50 values of 58.88 and 53.08μmol / L for 2 and 3, respectively The IC50 of Hep G2 were 83.95 and 44.74μmol / L, respectively. Conclusions A one-pot synthesis method with mild reaction conditions and simple post-treatment is explored. Of the 3 target complexes synthesized, compounds 2 and 3 showed moderate activity against A549 and Hep G2 cells.