摘要：Obesity has become a global threat to health;however,the available drugs for treating obesity are *** investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative *** short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte ***,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore ***,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse ***-ATS showed higher specificity for adipocyte targetability without obvious ***-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS *** conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.

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.

摘要：Anisotanols A—D(1-4),four new compounds possessing an unprecedented sesquiterpenoid skeleton with a congested tricyclic 6/3/5 ring system,were obtained from Anisodus *** structures were elucidated by comprehensive spectroscopic techniques,and the absolute configurations were confirmed via ECD calculations and single-crystal X-ray diffractions.A putative biosynthetic pathway for these compounds was *** evaluation disclosed that compound 3 showed anti-angiogenic activity by inhibiting the viability,migration,and tube formation in HUVECs.