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991.
Kwon SW Kang SK Lee JH Bok JH Kim CH Dal Rhee S Jung WH Kim HY Bae MA Song JS Ha DC Cheon HG Kim KY Ahn JH 《Bioorganic & medicinal chemistry letters》2011,21(1):435-439
A new series of thiazolidine derivatives with an adamantyl group was synthesized and evaluated for their ability to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Our initial compound 5a showed a weak inhibitory activity. Significant improvements in potency were achieved by substituent modification. The potent compound 8g (E) showed good in vitro inhibitory activity toward human 11β-HSD1, selectivity toward 11β-HSD2, metabolic stability, pharmacokinetic, and safety profile. Furthermore, this compound significantly inhibited 11β-HSD1 activity in rat and monkey models, and showed improved glycemic control in KKAy mice. 相似文献
992.
Parkinson’s disease (PD) is a late-onset neurodegenerative disease which occurs at more than 1% in populations aging 65-years and over. Recently, leucine-rich repeat kinase 2 (LRRK2) has been identified as a causative gene for autosomal dominantly inherited familial PD cases. LRRK2 G2019S which is a prevalent mutant found in familial PD patients with LRRK2 mutations, exhibited kinase activity stronger than that of the wild type, suggesting the LRRK2 kinase inhibitor as a potential PD therapeutics. To develop such therapeutics, we initially screened a small chemical library and selected compound 1, whose IC50 is about 13.2 μM. To develop better inhibitors, we tested five of the compound 1 derivatives and found a slightly better inhibitor, compound 4, whose IC50 is 4.1 μM. The cell-based assay showed that these two chemicals inhibited oxidative stress-induced neurotoxicity caused by over-expression of a PD-specific LRRK2 mutant, G2019S. In addition, the structural analysis of compound 4 suggested hydrogen bond interactions between compound 4 and Ala 1950 residue in the backbone of the ATP binding pocket of LRRK2 kinas domain. Therefore, compound 4 may be a promising lead compound to further develop a PD therapeutics based on LRRK2 kinase inhibition. 相似文献
993.
Kim S Song YH Lee JY Choi SR Dhandapani V Jang CS Lim YP Han T 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(7):1183-1192
Inheritance of resistance to downy mildew (Hyaloperonospora parasitica) in Chinese cabbage (Brassica rapa ssp. pekinensis) was studied using inbred parental lines RS1 and SS1 that display strong resistance and severe susceptibility, respectively. F(1), F(2), and BC(1)F(1) populations were evaluated for their responses to downy mildew infection. Resistance to downy mildew was conditioned by a single dominant locus designated BrRHP1. A random amplified polymorphic DNA (RAPD) marker linked to BrRHP1 was identified using bulked segregant analysis and two molecular markers designated BrPERK15A and BrPERK15B were developed. BrPERK15B was polymorphic between the parental lines used to construct the reference linkage map of B. rapa, allowing the mapping of the BrRHP1 locus to the A1 linkage group. Using bacterial artificial chromosome clone sequences anchored to the A1 linkage group, six simple polymerase chain reaction (PCR) markers were developed for use in marker-assisted breeding of downy mildew resistance in Chinese cabbage. Four simple PCR markers flanking the BrRHP1 locus were shown to be collinear with the long-arm region of Arabidopsis chromosome 3. The two closely linked flanking markers delimit the BrRHP1 locus within a 2.2-Mb interval of this Arabidopsis syntenic region. 相似文献
994.
995.
Trematoda Artyfechinostomumn sufratyfex Lane, 1915 was found in different mammal species of Southern Vietnam. Original measurements of this species from domestic pig, black rat, and Asian palm civet are given. 相似文献
996.
Sapkota K Roh E Lee E Ha EM Yang JH Lee ES Kwon Y Kim Y Na Y 《Bioorganic & medicinal chemistry》2011,19(7):2168-2175
In order to develop potent skin whitening agents, we have synthesized 17 hydroxyphenyl benzyl ether compounds and tested their melanin synthesis inhibitory activity, DPPH free radical scavenging activity and tyrosinase inhibitory activity. Compounds 32, 35 and 36 possessing 4-hydroxyphenyl benzyl ether structure showed excellent inhibitory capacity with almost 50-fold than arbutin used as a reference in the inhibition test of α-MSH stimulated melanin synthesis in B-16 cells. 4-Hydroxyphenyl benzyl ether compounds also showed good antioxidant activity in the DPPH free radical scavenging test. The tyrosinase function was effectively inhibited by 3,5-dihydroxyphenyl benzyl ether analogues, especially compounds 18, 22, and 24. 相似文献
997.
RecA binds to single-stranded (ss) DNA to form?a helical filament that catalyzes strand exchange with a homologous double-stranded (ds) DNA. The study of strand exchange in ensemble assays is limited by the diffusion limited homology search process, which masks the subsequent strand exchange reaction. We developed a single-molecule fluorescence assay with a few base-pair and millisecond resolution that can separate initial docking from the subsequent propagation of joint molecule formation. Our data suggest that propagation occurs in 3?bp increments with destabilization of the incoming dsDNA and concomitant pairing with the reference ssDNA. Unexpectedly, we discovered the formation of?a dynamic complex between RecA and the displaced DNA that remains bound transiently after joint molecule formation. This finding could have important implications for the irreversibility of strand exchange. Our model for strand exchange links structural models of RecA to its catalytic function. 相似文献
998.
In many clinical trials both repeated measures data and event history data are simultaneously observed from the same subject. These two types of responses are usually correlated, because they are from the same subject. In this article, we propose a joint model for the combined analysis of repeated measures data and event history data in the framework of hierarchical generalized linear models. The correlation between repeated measures and event time is modelled by introducing a shared random effect. The model parameters are estimated using the hierarchical‐likelihood approach. The proposed model is illustrated using a real data set for the renal transplant patients. 相似文献
999.
1000.
An infectious hepatitis C virus (HCV) cDNA clone (JFH1) was generated recently. However, quantitative analysis of HCV infection and observation of infected cells have proved to be difficult because the yield of HCV in cell cultures is fairly low. We generated infectious HCV clones containing the convenient reporters green fluorescent protein (GFP) and Renilla luciferase in the NS5a-coding sequence. The new viruses responded to antiviral agents in a dose-dependent manner. Responses of individual cells containing HCV to alpha interferon (IFN-alpha) were monitored using GFP-tagged HCV and time-lapse confocal microscopy. Marked variations in the response to IFN-alpha were observed among HCV-containing cells. 相似文献