Jing Yue, Wang Gang, Ge Ying, Xu Minjie, Gong Zhunan
Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
Molecules. 2015 Apr 21;20(4):7309-24. doi: 10.3390/molecules20047309.
Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4-10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11-17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.
已合成了15种积雪草苷（AA）的半合成衍生物，并对其生物活性进行了评估。利用核磁共振（NMR）、质谱（MS）和红外光谱（IR）证实了这些化合物在C-2、C-3、C-23和C-28位的成功修饰。此外，使用不同的癌细胞系（HeLa、HepG2、B16F10、SGC7901、A549、MCF7和PC3）在体外评估了它们的抗肿瘤作用，同时使用幼虫斑马鱼模型在体内评估了它们的抗血管生成活性。在这些衍生物中，化合物4-10显示出比AA更强的细胞毒性和抗血管生成作用，而化合物11-17的作用明显较小。由于新衍生物10可能用于局部用药，因此将其纳入成品制剂中，使用高效液相色谱法（HPLC）评估其稳定性。衍生物10的抗肿瘤活性明显优于AA和其他衍生物，其稳定性与其母体化合物AA相似。
