82821-39-4Relevant academic research and scientific papers
Glycyrrhetinic acid derivatives containing aminophosphonate ester species as multidrug resistance reversers that block the NF-κB pathway and cell proliferation
Jin, Le,Zhang, Bin,Hua, Shixian,Ji, Min,Huang, Xiaochao,Huang, Rizhen,Wang, Hengshan
, p. 3700 - 3707 (2018)
Novel NF-κB inhibitors based on Glycyrrhetinic acid (GA) derivatives containing aminophosphonate ester moieties were rationally designed and synthesized as well as evaluated their antitumor activities using MTT assay. Many target compounds showed potent antitumor activities against the tested human cancer cell lines including cisplatin-resistant cells, and exhibited significant inhibitory activity to the NF-κB with IC50 values at micromolar concentrations in A549 cells, respectively. Among them, compound 12e possessed excellent antitumor activities against the tested human cancer cell lines and showed low cytotoxicity toward to human normal liver cells. Moreover, 12e caused obvious loss of MMP and significantly induced ROS production, and displayed inhibition of cell migration against A549 cells in vitro. Importantly, 12e arrested the cell cycle at the S phases and ultimately induced cell apoptosis in A549 cells through blockage of NF-κB signaling pathway. Our research provided an efficient strategy for targeting NF-κB antitumor drug development.
Synthesis, mechanisms of action, and toxicity of novel aminophosphonates derivatives conjugated irinotecan in vitro and in vivo as potent antitumor agents
Huang, Rizhen,Huang, Xiaochao,Kong, Jing,Wang, Hengshan,Wang, Meng,Wang, Yanming,You, Qinghong,Yu, Chunhao,Zhang, Haijiang
, (2020/01/23)
Twenty novel aminophosphonates derivatives (5a-5j and 6a-6j) conjugated irinotecan were synthesized through esterification reaction, and evaluated their anticancer activities using MTT assay. In vitro evaluation revealed that they displayed similar or superior cytotoxicity compared to the positive drug irinotecan against A549, MCF-7, SK-OV-3, MG-63, U2OS and multidrug-resistant (MDR) SK-OV-3/CDDP cancer cell lines. Among them, 9b displayed the most potent activity, with IC50 values of 0.92–3.23 μM against five human cancer cells, which exhibited a 5.4–19.1-fold increase in activity compared to the reference drug irinotecan, respectively. Moreover, cellular mechanism studies suggested that 9b arrested cell cycle at S stage and induced cell apoptosis along with the decrease of mitochondrial membrane potential (MMP). Interestingly, 9b significantly inhibited tumor growth in SK-OV-3 xenograft models in vivo without apparent toxicity, which was better than the positive drug irinotecan. Taken together, 9b possessed potent antitumor activity and may be a promising candidate for the potential treatment of human ovarian cancer cells.
