Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia St., Nanjing 210009, China.
ChemMedChem. 2013 May;8(5):812-8. doi: 10.1002/cmdc.201200559. Epub 2013 Mar 20.
A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics.
从市售的贝壳杉烷型或托品烷型冬凌草甲素出发，通过实用且高效的合成方法，构建了一个有前途的表鬼臼毒素 14-O-二萜衍生物库。这些合成衍生物的抗增殖活性针对一组四种人类癌细胞系进行了评估。IC50 值与母体分子和紫杉醇（后者用作阳性对照）相似或优于紫杉醇。进一步研究了化合物 29 对人肝癌 Bel-7402 细胞的凋亡特性，以更好地了解其作用模式。此外，在胃癌（MGC-803 小鼠）小鼠模型的研究中，化合物 29 表现出很强的体内抗肿瘤活性。这些结果证明了这些基于二萜的类似物作为潜在的新型抗癌化疗药物进行进一步临床前研究的合理性。
