Shen Qing-Kun, Chen Zheng-Ai, Zhang Hong-Jian, Li Jia-Li, Liu Chuan-Feng, Gong Guo-Hua, Quan Zhe-Shan
a Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy , Yanbian University , Yanji , China.
b Department of Pharmacology , Medical School of Yanbian University , Yanji , China.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):324-333. doi: 10.1080/14756366.2017.1419219.
To identify anticancer agents with higher potency and lower toxicity, a series of oridonin derivatives with substituted benzene moieties at the C17 position were designed, synthesised, and evaluated for their antiproliferative properties. Most of the derivatives exhibited antiproliferative effects against AGS, MGC803, Bel7402, HCT116, A549, and HeLa cells. Compound 2p (IC= 1.05 µM) exhibited the most potent antiproliferative activity against HCT116 cells; it was more potent than oridonin (IC = 6.84 µM) and 5-fluorouracil (5-FU) (IC= 24.80 µM). The IC value of 2p in L02 cells was 6.5-fold higher than that in HCT116 cells. Overall, it exhibited better selective antiproliferative activity and specificity than oridonin and 5-FU. Furthermore, compound 2p arrested HCT116 cells at the G2 phase of the cell cycle and increased the percentage of apoptotic cells to a greater extent than oridonin.
为了鉴定具有更高效力和更低毒性的抗癌剂，设计、合成了一系列在C17位带有取代苯部分的冬凌草甲素衍生物，并对其抗增殖特性进行了评估。大多数衍生物对AGS、MGC803、Bel7402、HCT116、A549和HeLa细胞表现出抗增殖作用。化合物2p（IC=1.05μM）对HCT116细胞表现出最有效的抗增殖活性；它比冬凌草甲素（IC=6.84μM）和5-氟尿嘧啶（5-FU）（IC=24.80μM）更有效。2p在L02细胞中的IC值比在HCT116细胞中高6.5倍。总体而言，它比冬凌草甲素和5-FU表现出更好的选择性抗增殖活性和特异性。此外，化合物2p使HCT116细胞停滞在细胞周期的G2期，并且比冬凌草甲素更大程度地增加了凋亡细胞的百分比。
