异海松酸杂环酰胺衍生物的制备及抗癌活性

为了获得结构新型的抗肿瘤药物分子结构，以天然产物异海松酸为母核结构，合成了9个异海松酸基杂环酰胺化合物（Ⅱa～Ⅱi），其结构经FTIR、1H NMR、13C NMR和TOF-MS分析确证。抗肿瘤活性测试结果表明，所有目标化合物的抗肿瘤活性均比母体化合物异海松酸的活性高，尤其是含有吡嗪杂环的化合物Ⅱd对A375细胞表现出显著的增殖抑制活性，其IC50值为13.34 μmol/L，有望通过进一步结构修饰来提高活性成为异海松酸类抗癌先导化合物。

Preparation and anticancer activity of isopimaric acid heterocyclic amide derivatives

In order to obtain new molecular structure of antitumor drugs, nine heterocyclic amide compounds (Ⅱa ~ Ⅱi) were synthesized by using natural product isopimaric acid as the parent structure. The structures of target compouds were confirmed by FTIR, 1H NMR, 13C NMR and TOF-MS. The anti-tumor activity test results revealed that all target compounds showed higher anti-tumor activities than the parent compound isopimaric acid. Especilly, the compound Ⅱd containing pyrazine heterocycles showed significant cell proliferation inhibitory activity against A375 cells, and its IC50 value was 13.34 μmol / L. It is expected to become an anti-tumor lead compound of isopimaric acid by further structural modification to improve its activity.