黄芩苷铜和铝配合物的合成及其生物活性研究

Synthesis of baicalin-copper and baicalin-aluminium complex and its bioactivity

目的:合成黄芩苷铜和铝配合物,并研究其抗菌抗肿瘤活性和对巨噬细胞抗肿瘤作用的影响。方法:将黄芩苷在弱碱条件下与金属盐反应得到黄芩苷铜和黄芩苷铝配合物,倍比稀释法考察黄芩苷及其配合物对金黄色葡萄球菌、枯草杆菌、大肠杆菌、沙门氏菌和白色念珠菌的抑制作用;MTT法测定化合物对A549,HepG2的IC50和对小鼠腹腔巨噬细胞抗肿瘤作用的影响;中性红法测定化合物对巨噬细胞吞噬作用的影响。结果:反应所得黄芩苷铜和黄芩苷铝的产率分别为73.93%,91.08%,黄芩苷铜(黄芩苷铝)对上述菌的MIC(mol.L-1)分别为0.000 4(0.001 1),0.000 9(0.001 1),0.000 4(0.001 1),0.000 9(0.001 1),0.000 4(0.000 5),黄芩苷铜(黄芩苷铝)对A549,HepG2的IC50(μmol.L-1)分别为89.6(138.8),22.6(97.2),巨噬细胞经160μmol.L-1的黄芩苷、黄芩苷铜和黄芩苷铝作用后对A549的抑制率分别为43.52%,80.89%,52.66%。结论:小鼠急性毒性试验表明配合物无毒,抗菌抗肿瘤活性及对巨噬细胞抗肿瘤作用均为黄芩苷铜>黄芩苷铝>黄芩苷。

Objective： To study synthesis of baicalin-copper and baicalin-aluminium complex and its antimicrobial,anti-tumor activity and anti-tumor effect against macrophages.Method： Baicalin was reacted with metallic salt under a weak base condition to produce baicalin-copper and baicalin-aluminium complex.Baicalin and its synthesized complex were detected for antimicrobial activity against Staphylococcus aureus,Hay bacillus,Escherichia coli,Salmonella and Candida albicans by twofold broth dilution technique.Their anti-tumor activity against A549 and IC50 of HepG2 cells and anti-tumor effect against macrophages were detected by the MTT.And their phagocytic effect on macrophages was determined by the neutral red assay.Result： The yields of baicalin-copper and baicalin-aluminium complex were 73.93% and 91.08%,respectively.The minimum inhibitory concentration（MIC） value against Staphylococcus aureus,Hay bacillus,Escherichia coli,Salmonella and Candida albicans was 0.000 4,0.000 9,0.000 4,0.000 9,0.000 4 mol·L^-1for baicalin-copper complex and 0.001 1,0.001 1,0.001 1,0.001 1,0.000 5 mol·L^-1for baicalin-aluminium complex.The IC50 values against A549 and HepG2 cells were 89.6,22.6 μmol·L^-1for baicalin-copper complex,and 138.8,97.2 μmol·L^-1for baicalin-aluminium complex.The inhibitory ratio of macrophage on A549 cell was 43.52%,80.89%,52.66%,respectively,after the macrophages were stimulated by baicalin,baicalin-copper and baicalin-aluminium complex at a concentration of 160 μmol·L^-1Conclusion： The acute toxicity test in mice showed that the complex was nontoxic to mice.Baicalin-copper complex showed the highest antimicrobial,anti-tumor activity,and the strongest effect on the anti-tumor activity of macrophage,while baicalin showed the lowest activities compared with baicalin-copper and baicalin-aluminium complex.