Combination of chemotherapy and gaseous signaling molecular therapy: Novel β-elemene nitric oxide donor derivatives against leukemia.
Junlong ZhuXiaoying JiangXinyu LuoRui ZhaoJunjie LiHong CaiXiang-Yang YeRenren BaiTian XiePublished in: Drug development research (2023)
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.
Keyphrases
- nitric oxide
- induced apoptosis
- body weight
- acute myeloid leukemia
- cell cycle arrest
- bone marrow
- chronic myeloid leukemia
- endothelial cells
- endoplasmic reticulum stress
- high fat diet induced
- nitric oxide synthase
- molecular dynamics
- signaling pathway
- squamous cell carcinoma
- hydrogen peroxide
- metabolic syndrome
- climate change
- adipose tissue
- skeletal muscle
- insulin resistance