4-β-酯取代-4-脱氧-4′-去甲表鬼臼毒素衍生物的合成及其抗肿瘤活性

SYNTHESIS AND ANTITUMOR ACTIVITY OF 4-β-ALKOXYLCARBONYL-4-DEOXY-4′-DEMETHYLEPIPODOPHYLLOTOXIN

摘要: 目的　寻找高效低毒的抗肿瘤药物。方法和结果　本文设计并合成了新的C₄位β构型的酯取代的衍生物38个(II-1～II-38)，并进行了体外对L₁₂₁₀细胞和KB细胞的抗肿瘤活性实验。结论　脂肪酯的活性强于芳香酯，其中以II-10的活性最强，超过etoposide 2个数量级。脂肪酯中主链不超过3个碳原子的活性较好。在芳香酯中，苯环上连接吸电子基的化合物的活性稍强于连接有供电子基的化合物。

Abstract: AIM　To search for more potential and lower toxicity antitumor drugs. METHODS AND RESULTS　Thirty eight new 4-β-ester substituted-4-deoxy-4′-demethylepipodophylotoxin derivatives(II-1～II-38) were designed and synthesized. All compounds were screened in vitro against L1210 leukemia and KB cells. CONCLUSION　Fatty esters showed higher activity than aromatic esters. II-10 exhibited the highest activity, which is more than 100-fold of etoposide. For fatty esters, the compounds with less than 3 carbons in the main chain have higher activity, while for aromatic esters, those having electron-attracting substituents in the aromatic ring are more active.