摘要：A series of novel bone-targeting antitumor agents-the conjugates of 5-fluorouracil and hydroxybisphosphonate were designed and synthesized their structures were confirmed by ^1H-NMR, ^13C-NMR, ^31P-NMR, MS, and element analysis. The tests of bone-targeting activity show that these compounds have an obvious affinity for bone.

摘要：A series of glucose-cholesterol derivatives 8a-8e as ligands for brain targeting liposomes were synthesized. The preparation of compound 6 involved temporary protection of glucose with chlorotrimethylsilicane and hexamethyldisilazane followed by selectively hydrolyzed. The known cholesteryl tosylate 1 were coupled to ethylene glycols to afford alcohol 2a-2e. Substitution and deprotection of alcohol 2a-2e furnished the acids 4a-4e, which was condensed with compound 6 to get compounds 7a-7e, and then was deprotected in tetrahydrofuran with TFA to obtain the title compounds. As a model drug, tegafur was entrapped by liposomes coupled with 8b, and preliminary in vivo evaluation shown 8b could enhance the ability of liposomes delivering tegafur across the blood brain barrier.

摘要：A series of 1-oxacephem analogs were synthesized and their antibacterial properties against five strains of Gram-positive and Gram-negative bacteria were evaluated in vitro while ceftazidine was selected as *** of the tested compounds,compound 12c in particular,showed more active against three selected strains than the standard.

摘要：In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M *** differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert *** ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport *** differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen(SLAA)and integrinβ1,and down-regulated activity of alkaline *** targeting M cells with iRGD peptide(cRGDKGPDC),the transport of nanoparticles *** vivo,the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal *** the evaluation of immune effect in vivo,the nasal administration of OVA-PLGA/iRGD led to more release of IgG,IFN-γ,IL-2 and secretory IgA(sIgA)compared with OVA@PLGA ***,the study constructed in vitro M cell model,and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.

摘要：多重耐药细菌引发的肺部感染对人类健康构成了严重威胁.细菌生物膜加剧了肺部感染的持续和复发,限制了抗生素的可及性和有效性.基于凝集素竞争策略和颗粒表面修饰策略,本研究设计了一种硫酸多粘菌素B(PMBS)的吸入粉雾剂(DPI)用于治疗肺部感染.该制剂的载体是具有高凝集素亲和性(HLA)的小分子糖(如棉子糖),可靶向细菌凝集素,限制生物膜的扩展.该制剂的粒径约为3μm,其表面褶皱程度和药物与载体的比例有关.处方F_(5)(PMBS:棉子糖=10:90)表现出最高的微细粒子分数(FPF=64.86%),表明其具备显著增强的肺部药物递送效率.通过添加棉子糖,制剂在抑制生物膜形成和清除成熟生物膜方面的效果显著提高.在急性和慢性肺部感染的大鼠模型中,相较于喷雾干燥的PMBS,处方F_(5)表现出更强的抗菌效果,并引起更低炎症反应.综上,基于HLA载体的抗生素DPI具有治疗细菌生物膜相关肺部感染的良好前景.

摘要：Simultaneous inhibition of MDM2 and CDK4 may be an effective treatment against glioblastoma. A collection of chiral spirocyclic tetrahydronaphthalene(THN)-oxindole hybrids for this purpose have been developed. Appropriate stereochemistry in THN-fused spirooxindole compounds is key to their inhibitory activity: selectivity differed by over 40-fold between the least and most potent stereoisomers in time-resolved FRET and KINOMEscan~? in vitro assays. Studies in glioblastoma cell lines showed that the most active compound ent-4g induced apoptosis and cell cycle arrest by interfering with MDM2-P53 interaction and CDK4 activation. Cells treated with ent-4g showed up-regulation of proteins involved in P53 and cell cycle pathways. The compound showed good anti-tumor efficacy against glioblastoma xenografts in mice. These results suggested that rational design, asymmetric synthesis and biological evaluation of novel tetrahydronaphthalene fused spirooxindoles could generate promising MDM2-CDK4 dual inhibitors in glioblastoma therapy.