Design,synthesis and biological evaluation of novel series of 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold derivatives as PI3Kα inhibitors

The abnormal activation of PI3K signaling pathway leads to the occurrence of various cancers. The PI3Kα is frequently mutated and overexpressed in many human cancers. Therefore, the PI3Kα was considered as a promising target in therapeutic treatment of cancer. In this study, two series of compounds containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold were synthesized and evaluated antiproliferative activities against three cancer cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most potent antiproliferative activity was selected for further evaluation on normal cells and PI3K kinase. Studies indicated that compound 7f could decrease the phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding interactions were found in the docking of 7f with PI3K enzyme. All the results suggested that 7f was a potent PI3Kα inhibitor.     

蓖麻籽提取液对福寿螺毒杀效果及作用机制

采用生物浸泡法, 以草本植物蓖麻籽提取液制备植物源毒杀剂, 研究不同提取液浓度(0、0.5、1.5、3.0、4.5、6.0 g/L)对福寿螺(Pomacea canaliculata Lam)毒杀作用效果, 并通过福寿螺在亚致死浓度1.58(LC₂₅)、3.82(LC₅₀)和6.05 g/L(LC₇₅) 处理条件下的肝脏组织生理生化指标及其相关性, 进一步分析其毒杀作用机制。结果表明: 在提取液处理48h后, 福寿螺死亡率随着时间延长和浓度的增加而增加, 且各浓度处理下福寿螺死亡率差异显著(P<0.05)。福寿螺在亚致死浓度处理48h后, 其肝胰腺组织中蛋白质含量(TP)、丙二醛(MDA)含量和过氧化氢酶(CAT)活性与对照组均存在差异, 过氧化氢酶(CAT)活性与丙二醛(MDA)含量呈显著负相关关系(P<0.05)。蓖麻籽提取液通过影响福寿螺肝脏组织中蛋白质含量(TP)和丙二醛(MDA)含量, 及过氧化氢酶(CAT)活性, 导致螺肝脏组织损伤, 机体代谢紊乱, 从而达到毒杀效果。     

小黑杨PsnHB22基因在烟草中的遗传转化研究

HD-Zip转录因子在光信号转导、非生物胁迫、叶片发育等方面发挥重要的作用，HB22转录因子是HD-ZipⅠ亚家族的成员之一。为研究PsnHB22基因的功能，从小黑杨（Populus simonii×P.nigra）cDNA中克隆PsnHB22基因并构建植物表达载体进行烟草（Nicotiana tabacum）的遗传转化，以获得该基因过量表达的转基因株系。对转基因株系进行PCR、qRT-PCR分子检测后观察表型，结果显示在营养生长时期，转基因烟草叶片窄小并且株高显著低于野生型对照。测定转基因烟草及野生型叶片的叶绿素含量，发现转基因烟草叶绿素含量显著高于野生型。由此推测PsnHB22基因在植株高生长、光合作用及叶片的形态建成等过程中起着重要的作用。