Combination of chemotherapy and gaseous signaling molecular therapy: Novel β‐elemene nitric oxide donor derivatives against leukemia

作者：Junlong Zhu, Xiaoying Jiang, Xinyu Luo, Rui Zhao, Junjie Li, Hong Cai, Xiang‐Yang Ye, Renren Bai, Tian Xie · 发表于：Drug Development Research · 年份：2023 · DOI：10.1002/ddr.22051 · 被引用次数：97 · 研究领域：Genomics, phytochemicals, and oxidative stress、Synthesis and biological activity、Bioactive Compounds and Antitumor Agents

Abstract This study aimed to design and synthesize active hybrids of β ‐elemene and nitric oxide (NO) donor pharmacophore as potential agents for treating leukemia. Derivatives reported herein exerted better inhibitory effects against human chronic myeloid leukemia K562 cells compared to β ‐elemene (IC 50 > 100 μM). The most potent compound 18f showed an IC 50 value of 0.53 μM against K562 cells, as well as a high NO release level in vitro. In the K562 xenograft tumor mice model, compound 18f effectively inhibited the growth of the tumor, with a significant inhibition rate of 73.18%. After treatment with compound 18f , the body weight of mice did not decrease, indicating that it possessed good safety profile. All these proved that compound 18f was an excellent potential agent against leukemia.