Synthesis and biological evaluation of artemisinin derivatives as potential MS agents

In this paper, a series of artemisinin derivatives were synthesized and evaluated. Studies have shown that IFN-gamma produced by Th1 CD4(+) T cells and IL-17A secreted by Th17 CD4(+) T cells played critical roles in the treatment of multiple sclerosis. We used different concentrations of artemisinin derivatives to inhibit Th1/Th17 differentiation in naive CD4(+) T cells and to characterize IFN-gamma / IL-17A in in vitro experiments. The preliminary screening results showed that ester compound 5 exhibited obvious inhibitory activities on Th1 and Th17 (IFN-gamma decreased from 41% to 3% and IL-17A decreased from 24% to 8% at the concentration of 10 nM to 10 mu M), and carbamate compounds also had obvious inhibitory activities against Th17 at high concentration. Moreover, we investigated the effect of compound 5 on myelin oligodendrocyte glycoprotein (MOG)-induced mice experimental autoimmune encephalomyelitis (EAE) model in vivo. 100 mg/kg compound 5 effectively reduced the disease severity of EAE compared with the vehicle group. This research revealed that compound 5 could be a promising avenue as potential MS inhibitor.

Automated summary

In this study, a series of artemisinin derivatives were synthesized and evaluated. The results showed that ester compound 5 exhibited significant inhibitory activities on Th1 and Th17 cells, while also reducing the disease severity in a mouse model of experimental autoimmune encephalomyelitis. This research suggests that compound 5 has potential as a therapeutic inhibitor for multiple sclerosis.