摘要：Acidic oligosaccharide sugar chain （AOSC）, a D-mannuronic acid oligosaccharide, derived from brownalgaepolysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer＇s Disease （AD） drug candidate. The identification of AOSC-binding protein（s） in neurons is very important for understanding its action mechanism. To determine the binding protein（s） of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry （LC-MS/MS） analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 （AP-2） and amyloid precursor protein （APP）. These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.

摘要：A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h *** docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.

摘要：A new series of isatin semicarbazide derivatives（7a-7j） were synthesized and characterized by spectroscopic means and elemental *** and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test *** ulcerogenicity was also determined for all the *** of the compounds showed moderate enhancement of the *** the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.

摘要：The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in *** was employed to estimate optimum dissolution and absorption rate of *** dissolution test was employed using pH 1.2,4.0,6.8 buffer solution,or water,to measure the in vitro release behaviors of nicorandil formulations.A single dose(15 mg)of each formulation was orally administered to four beagle dogs under fasted conditions,and the pharmacokinetic parameters were *** in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle *** was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release *** nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release *** release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extendedrelease *** results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

摘要：In order to find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogues containing a pyridine ring were synthesized and evaluated for their in vitro antifungal activity and water solubility. The results indicated that some compounds showed potent activity against six pathogenic fungi. In particular, the analogue 17a having an isobutyl substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of compound l？a was sufficiently improved over SYN-2869.

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.

摘要：In this study,we unveil a conceptual technology for fabricating artificial metalloenzymes(ArMs)by deeply integrating hemin into protein scaffolds via a protein refolding process,a method that transcends the conventional scope of surface-level *** approach involves denaturing proteins,such as benzaldehyde lyase,green fluorescent protein,and Candida antarctica lipase B,to expose extensive reactive amino acid residues,which are then intricately linked with hemin using orthogonal click reactions,followed by protein *** process not only retains the proteins’structural integrity but expands proteins’*** most notable outcome of this methodology is the hemin@BAL variant,which demonstrated a remarkable 83.7%conversion rate in cyclopropanation reactions,far surpassing the capabilities of traditional hemin-based catalysis in *** success highlights the significant role of protein structure in the ArMs’activity and marks a substantial leap forward in chemical modification of *** findings suggest vast potentials of protein refolding approaches for ArMs across various catalytic applications,paving the way for future advancements in synthetic biology and synthetic chemistry.

摘要：A series of new hybrids of dehydroandrographolide(TAD),a biologically active natural product,bearing nitric oxide(NO)-releasing moieties were synthesized and designated as NO-donor *** biological activities of target compounds were studied in human erythroleukemia K562 cells and breast cancer MCF-7 *** evaluation indicated that the most active compound I-5 produced high levels of NO and inhibited the proliferation of K562(IC_(50) 1.55μmol?L^(–1))and MCF-7(IC_(50)2.91μmol?L^(–1))cells,which were more potent than the lead compound TAD and attenuated by an NO *** conclusion,I-5 is a novel hybrid with potent antitumor activity and may become a promising candidate for future intensive study.

摘要：Since the PI3K signaling pathway is the most commonly activated in human cancers,inhibition of PI3K is a promising approach to cancer *** this study,a series of 2-methyl-5-nitrobenzeneacylhydrazones were designed and *** the new derivatives were tested by p110α enzymatic and Rh30 cellular *** enzyme selectivity profiling proved that 6e and 7 were potential selective PI3K inhibitors.

摘要：To discover an efficient route for the shift from an antibacterial fluoroquinolone to an antitumor one based on the mechanistic similarities between targeting topoisomerases and the eukaryotic ones,two series of the title compounds,C3 bis-oxadiazole methylsulfides 6a―6h and corresponding dimethylpiperazinium iodides 7a―7h derived from levofloxacin 1 were designed and *** in vitro antiproliferative activities against Chinese hamster ovary cell line（CHO）,murine leukemia cell line（L1210） and human leukocytoma cell line（HL60） were evaluated by MTT assay,and inhibitory effect on DNA topoisomerase IIα was also measured by means of densitometric assay.