School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, 200240 Shanghai, China.
Eur J Med Chem. 2011 Sep;46(9):3934-41. doi: 10.1016/j.ejmech.2011.05.065.
A series of novel β-hydroxyisovalerylshikonin analogues bearing oxygen-containing substituents at the side-chain hydroxyl of shikonin were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against multi-drug resistant (MDR) cell lines DU-145 and HeLa. Most compounds exhibited significant inhibitory activity on both cell lines. The structure-activity relationship showed the analogues with ether substituents displayed the most potent antitumour activity and selective cytotoxicity towards DU-145. Among the compounds with ether substituents, increasing the steric hindrance in the carbon bearing β-hydroxyl or replace the β-hydroxyl with acetoxy or methoxy would lead to the decline of cytotoxicity.
设计并合成了一系列新型的β-羟异戊酰紫草素类似物，它们在紫草素侧链羟基上带有含氧取代基。这些化合物的体外细胞毒性在多药耐药（MDR）细胞系 DU-145 和 HeLa 中进行了评估。大多数化合物对这两种细胞系均表现出显著的抑制活性。构效关系表明，带有醚取代基的类似物表现出对 DU-145 最有效的抗肿瘤活性和选择性细胞毒性。在带有醚取代基的化合物中，增加带有β-羟基的碳原子上的空间位阻或用乙酰氧基或甲氧基取代β-羟基会导致细胞毒性下降。
