异长叶烷基吡唑类衍生物的合成及其抗肿瘤、抗炎活性研究

Synthesis,Antitumor and Anti-inflammatory Activities of Isolongifolanonyl Pyrazole Derivatives

以异长叶烷酮为原料,采用叔丁醇钾为催化剂,与芳香醛进行羟醛缩合反应合成中间体2a^2j,再与水合肼进行缩合、环化和脱氢芳构化反应,得到异长叶烷基吡唑类衍生物3a^3j,终产物的得率为69.5%~76.5%.采用1H NMR,13C NMR,IR,MS和元素分析表征了化合物的结构,通过X射线衍射分析测定了化合物3i的晶体结构.对合成所得化合物进行了抗炎活性、抗肿瘤活性测定.结果表明,化合物3h与3i对人脐静脉内皮细胞(HUVECs)表现出显著的抗炎活性,其IC50值分别为(15.42±0.6)和(4.74±0.3)μmol/L,化合物3a,3c,3e,3j对人体肝癌细胞(HepG2)具有体外抗肿瘤活性,其IC50分别为(5.27±0.5),(6.71±0.4),(4.68±0.2)和(4.57±0.5)μmol/L.

A series of new isolongifolanonyl pyrazole derivatives 3a-3j were synthesized by aldol-condensation, cyclization and dehydroaromatization from isolongifolanone. The yields of products ranged from 69.5% to 76.5%. The chemical structures of compounds obtained were elucidated by 1H NMR, 13C NMR, IR, MS spectra and elemental analysis. The strucure of compound 3i was determined by X-ray single crystal diffraction. Their inhibitory activities against human hepatoma cell （HepG2） and human umbilical vein endothelial cell （HUVECs） were evaluated. The results indicated that compounds 3h and 3i[IC50=（15.42±0.6）, （4.74±0.3） μmol/L] showed obvious inhibitory activity against HUVECs. Compounds 3a, 3c,3e and 3j[IC50=（5.27±0.5）, （6.71±0.4）, （4.68±0.2）, （4.57±0.5）] μmol/L showed better antitumor activity against HepG2.