硫化氢供体型去氢枞酸衍生物的合成及其细胞毒性

Synthesis and Cytotoxic Activity of Dehydroabietic Acid Derivatives Bearing A H2S Donor

以去氢枞酸为原料,通过不同的长度碳链与硫化氢供体4-羟基硫代苯甲酰胺偶联,合成了5个新型硫化氢供体型去氢枞酸衍生物,所得化合物结构经^(1)H NMR、^(13)C NMR和HR-MS表征。以阿霉素为阳性对照药,采用MTT法测定目标化合物对人肝癌细胞(HepG2)、人胃癌细胞(MGC803)、人膀胱癌细胞(T24)、人肺癌细胞(A549)和人正常肝细胞(LO2)的细胞抑制作用。结果表明:大部分化合物对4种肿瘤细胞株的抑制活性优于母体化合物去氢枞酸,其中化合物4c对HepG2、T24和A549细胞株的IC_(50)值分别为4.63±0.18、6.06±0.49和5.79±0.14μmol·L^(-1),优于或接近阳性对照药阿霉素(5.44±0.87、3.69±0.78和3.75±0.11μmol·L^(-1))。

In order to search for novel candidate compounds with better antitumor activities,five dehydroabietic acid derivatives bearing a H2S donor were synthesized by coupling 4-hydroxythiobenzamide with dehydroabietic acid via various linkers.Structures of all target compounds were determined by^(1)H NMR,^(13)C NMR,and HR-MS.The cytotoxicity of synthetic derivatives against human liver cancer cells(HepG2),human gastric cancer cells(MGC803),human bladder cancer cells(T24),human lung cancer cells(A549),and human normal liver cells(LO2)were assessed by MTT assay using doxorubicin as positive control.Preliminary assay results showed that the most of target compounds exhibited stronger inhibitory effects against tested tumor cell lines than the parent compound dehydroabietic acid.Among them,compound 4c was the most potent one,with IC_(50)values against HepG2,A549 and T24 cell lines being 4.63±0.18,6.06±0.49 and 5.79±0.14μmol·L^(-1),respectively,which were superior or comparable to doxorubicin(5.44±0.87、3.69±0.78 and 3.75±0.11μmol·L^(-1)).