磷脂酰肌醇-3-激酶(PI3K)抑制剂 XL765的合成

目的 对磷脂酰肌醇-3-激酶(PI3K)抑制剂XL765进行合成工艺研究。方法 以邻苯二胺、草酸为起始原料经过环合、氯代、氯磺化、磺酰化、取代、还原以及酰胺化制得XL765。结果与结论 经过6步反应合成目标化合物XL765,化学结构经1H-NMR及MS确证。对其中多步反应条件进行了工艺考察及优化,总收率为31.5%(以邻苯二胺计),高于文献报道收率(25.5%)。     

C5a/C5aR通路对约氏疟原虫增殖和小鼠生存的影响

目的观察C5a/C5aR通路对约氏疟原虫17XL(P.y17XL)的增殖及其对BALB/c小鼠致死率的影响。结论将实验小鼠分为正常BALB/c组和C5aR-/-BALB/c组,每组5只,相同剂量的P.y17XL(2×105)分别感染正常BALB/c组小鼠和C5aR-/-BALB/c组小鼠,于感染后0、2、4和6d观察两组小鼠原虫血症和存活率的变化,并且采用ELISA检测感染P.y17XLBALB/c小鼠血清中C5a的水平。结果与正常组小鼠相比,C5aR-/-组小鼠生存期缩短,P.y17XL在C5aR-/-组小鼠的原虫血症较野生株小鼠高(P<0.05),而P.y17XL感染小鼠的血清中C5a含量低于未感染的小鼠。结论 C5a/C5aR能够抑制P.y17XL的增殖,并能延长感染小鼠的生存期。     

Involvement of p38 mitogen‐activated protein kinase pathway in honokiol‐induced apoptosis in a human hepatoma cell line (hepG2)

Background: Honokiol has been known to have antitumour activity. This study was conducted to evaluate the antiproliferative potential of honokiol against the hepG2 heptocellular cell line and its mechanism of action. Methods: hepG2 cells were treated with honokiol of 0–40 μg/ml concentration. The cytotoxic effect of honokiol was determined by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The apoptosis was evaluated by flow cytometry. Western blots were used to analyse the expression of various proteins (procaspase‐9, procaspase‐3, cleaved caspase‐3, cytochrome c, Bcl‐2, Bax, Bad, Bcl‐X_L and p38). Results: Honokiol induced apoptosis with a decreased expression of procaspase‐3 and ‐9 and an increased expression of active caspase‐3. Exposure of hepG2 cells to honokiol resulted in the downregulation of Bcl‐X_L and Bcl‐2 expression and the release of mitochondrial cytochrome c to the cytosol. In addition, honokiol activated the p38 mitogen‐activated protein kinase (MAPK) pathway, and the inhibition of this pathway by SB203580 reduced honokiol‐induced apoptosis and activation of caspase‐3. Conclusion: Honokiol induces apoptosis of hepG2 human hepatocellular carcinoma cells through activation of the p38 MAPK pathway, and, in turn, activation of caspase‐3.