| Autor: |
Ge W; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Ming W; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Li Z; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Tang Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Li YN; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Yang J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China., Hao X; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China.; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China., Yuan C; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, People's Republic of China.; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, People's Republic of China.; Natural Products Research Center of Guizhou Province, Guiyang 550014, People's Republic of China. |
| Abstrakt: |
Rocaglaol, embedding a cyclopenta[ b ]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, the drug-like properties of these compounds are poor. To improve the physicochemical properties of rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed and synthesized. These derivatives were tested for the inhibitory effects on three tumor cell lines, HEL, MDA-231, and SW480, using the MTT assay. Among them, 22 derivatives exhibited good cytotoxic activities with IC 50 values between 0.11 ± 0.07 and 0.88 ± 0.02 μM. Fourteen derivatives exhibited stronger cytotoxicity than the positive control, adriamycin. In particular, a water-soluble derivative revealed selective cytotoxic effects on HEL cells (IC 50 = 0.19 ± 0.01 μM). This compound could induce G1 cell cycle arrest and apoptosis in HEL cells. Western blot assays suggested that the water-soluble derivative could downregulate the expression of the marker proteins of apoptosis, PARP, caspase-3, and caspase-9, thus inducing apoptosis. Further CETSA and Western blot studies implied that this water-soluble derivative might be an inhibitor of friend leukemia integration 1 (Fli-1). This water-soluble derivative may serve as a potential antileukemia agent by suppressing the expression of Fli-1. |
