Synthesis and antitumor activity of 2-isocamphanyl thiosemicarbazone derivatives via ROS-enhanced mitochondrial damage.
Yunyun WangZhonglong WangHongbo KuangYan ZhangWen GuYongqiang ZhuShifa WangPublished in: Chemical biology & drug design (2019)
A series of novel 2-isocamphanyl thiosemicarbazone derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. In in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against four cancer cell lines (RPMI-8226, A549, MDA-MB-231, and HepG2 cancer cells) and showed low toxicity against human gastric mucosal cells (GES-1). Among them, compound 4h exhibited excellent antitumor activity against the tested cancer cells with IC50 values of 0.4, 1.1, 1.6, and 1.7 μM for MDA-MB-231, RPMI-8226, A549, and HepG2, respectively. Further, mechanism studies indicated that compound 4h induced apoptosis in MDA-MB-231 cells through enhancing reactive oxygen species levels, inducing mitochondrial membrane potential decrease, and influencing the expression of Bax, Bcl-2, caspase-3, and caspase-9.
Keyphrases
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- signaling pathway
- reactive oxygen species
- breast cancer cells
- cell cycle arrest
- dna damage
- cell death
- magnetic resonance
- high resolution
- poor prognosis
- endothelial cells
- structure activity relationship
- solid state
- squamous cell
- climate change
- long non coding rna
- human health
- induced pluripotent stem cells