Discovery and bioassay of disubstituted β-elemene-NO donor conjugates:synergistic enhancement in the treatment of leukemia  

作　　者：ZHU Junlong JIANG Xiaoying LUO Xinyu GAO Yuan ZHAO Rui LI Junjie CAI Hong DANG Xiawen YE Xiangyang BAI Renren XIE Tian 

机构地区：[1]School of Pharmacy,Hangzhou Normal University,Hangzhou 311121,China [2]Key Laboratory of Elemene Class Anti-cancer Chinese Medicines,Engineering Laboratory of Development and Application of Traditional Chinese Medicines,Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province,Hangzhou Normal University,Hangzhou 311121,China

出　　处：《Chinese Journal of Natural Medicines》2023年第12期916-926,共11页中国天然药物（英文版）

基　　金：This project was supported by the Natural Science Foundation of Zhejiang province(No.LY20H300004);the National Natural Science Foundation of China(Nos.82073686,81730108,and 81973635);Scientific Research Foundation for Scholars of HZNU(Nos.2021QDL026 and 2019QDL003);the Ministry of Science and Technology of China(High-end foreign experts program,Nos.G20200217005 and G2021017004).

摘　　要：Natural products are essential sources of antitumor drugs.One such molecule,β-elemene,is a potent antitumor compound extracted from Curcuma wenyujin.In the present investigation,a series of novel 13,14-disubstituted nitric oxide(NO)-donorβelemene derivatives were designed,withβ-elemene as the foundational compound,and subsequently synthesized to evaluate their therapeutic potential against leukemia.Notably,the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line,with a high NO release.In vivo studies indicated that compound 13d could effectively inhibit tumor growth,exhibiting no discernible toxic manifestations.Specifically,a significant tumor growth inhibition rate of 62.9%was observed in the K562 xenograft tumor mouse model.The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.

关 键 词：Antitumor activity Chronic myeloid leukemia Β-ELEMENE Nitric oxide donor Structural modification 

分 类 号：R284.2[医药卫生—中药学]