ABSTRACT
Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.
ABSTRACT
Objective To explore the effect of Orem self-care pattern on quality of life of patients undergoing radiotherapy after breast cancer operation.Methods One hundred patients undergoing radiotherapy after breast cancer operation were randomly divided into control group and treatment group in equal number.The control group was treated by conventional nursing.Orem self-control pattern was used in the treatment group besides conventional nursing.QOL scale was employed to observe their quality of life after radiotherapy.Result The self-care ability and quality of life of the treated group were improved significantly comparing with the control group(P<0.05,for both).Conclusion Orem self-care pattern can effectively improve the quality of life of patients undergoing radiotherapy after breast cancer operation by way of helping them actively completing function exercises on the diseased limbs and propelling their early rehabilitation.