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91.
Arlene A. Sy-Cordero Tyler N. Graf Scott P. Runyon Mansukh C. Wani David J. Kroll Rajesh Agarwal Scott J. Brantley Mary F. Paine Stephen J. Polyak Nicholas H. Oberlies 《Bioorganic & medicinal chemistry》2013,21(3):742-747
Flavonolignans from milk thistle (Silybum marianum) have been investigated for their cellular modulatory properties, including cancer chemoprevention and hepatoprotection, as an extract (silymarin), as partially purified mixtures (silibinin and isosilibinin), and as pure compounds (a series of seven isomers). One challenge with the use of these compounds in vivo is their relatively short half-life due to conjugation, particularly glucuronidation. In an attempt to generate analogues with improved in vivo properties, particularly reduced metabolic liability, a semi-synthetic series was prepared in which the hydroxy groups of silybin B were alkylated. A total of five methylated analogues of silybin B were synthesized using standard alkylation conditions (dimethyl sulfate and potassium carbonate in acetone), purified using preparative HPLC, and elucidated via spectroscopy and spectrometry. Of the five, one was monomethylated (3), one was dimethylated (4), two were trimethylated (2 and 6), and one was tetramethylated (5). The relative potency of all compounds was determined in a 72 h growth-inhibition assay against a panel of three prostate cancer cell lines (DU-145, PC-3, and LNCaP) and a human hepatoma cell line (Huh7.5.1) and compared to natural silybin B. Compounds also were evaluated for inhibition of both cytochrome P450 2C9 (CYP2C9) activity in human liver microsomes and hepatitis C virus infection in Huh7.5.1 cells. The monomethyl and dimethyl analogues were shown to have enhanced activity in terms of cytotoxicity, CYP2C9 inhibitory potency, and antiviral activity (up to 6-fold increased potency) compared to the parent compound, silybin B. In total, these data suggested that methylation of flavonolignans can increase bioactivity. 相似文献
92.
Westkaemper RB Runyon SP Savage JE Roth BL Glennon RA 《Bioorganic & medicinal chemistry letters》2001,11(4):563-566
Comparison of the serotonin 5-HT2A receptor affinities of a parallel series of structural analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine cyproheptadine suggests that the two agents bind to the receptor in different fashions. Examination of ligand-receptor model complexes supports the experimental data and suggests a potential origin for the differences in binding modes. 相似文献
93.
Runyon SP Savage JE Taroua M Roth BL Glennon RA Westkaemper RB 《Bioorganic & medicinal chemistry letters》2001,11(5):655-658
Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways. 相似文献
94.
A cytological basis for a map of the nucleolar chromosome in man 总被引:1,自引:0,他引:1
95.
International bacteriological code of nomenclature 总被引:1,自引:0,他引:1
96.
Distribution of individual members of the mosquito Anopheles maculipennis complex in Germany identified by newly developed real‐time PCR assays
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R. LÜHKEN C. CZAJKA S. STEINKE H. JÖST J. SCHMIDT‐CHANASIT W. PFITZNER N. BECKER E. KIEL A. KRÜGER E. TANNICH 《Medical and veterinary entomology》2016,30(2):144-154
Owing to their role as vectors of malaria parasites, species of the Anopheles maculipennis complex (Diptera: Culicidae) Meigen were intensively studied in the past, but with the disappearance of malaria in Germany in the middle of the last century, the interest in this field of research declined. A comprehensive ecological analysis of the current species distribution for Germany is lacking. Between 2010 and 2013, a total of 1445 mosquitoes of the An. maculipennis complex were collected at 72 different sites in Germany. The samples comprise 722 single individuals as well as 723 individuals in 90 pools of up to 25 mosquitoes. All samples were analysed with newly developed species‐specific qPCR assays for the identification of the four German species using nucleotide differences within the internal transcribed spacer 2 (ITS2) ribosomal DNA. All gathered data were used for species distribution modelling. The overall prevalence of An. messeae s.l. was highest with 98.89% of all pools; An. daciae with 6.93% of all individuals and An. messeae s.s. with 69.53%. The prevalence of the other two species was relatively low: An. maculipennis s.s. with 13.30% of all individuals (6.67% of all pools) and An. atroparvus with 1.80% of all individuals (1.11% of all pools). 相似文献
97.
Genetic signature of the colonisation dynamics along a coastal expansion front in the damselfly Coenagrion scitulum
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JANNE SWAEGERS JOACHIM MERGEAY AUDREY ST‐MARTIN GEERT DE KNIJF MAARTEN H. D. LARMUSEAU ROBBY STOKS 《Ecological Entomology》2015,40(4):353-361
1. Many insects are expanding their distribution range polewards as a result of climate change, which has been shown to be associated with founder effects leading to a reduction in genetic diversity and an increase in genetic differentiation. These spatial genetic patterns may arise from colonisation from a broad expansion front or a limited neighbourhood after a stepping stone model of dispersal. The temporal persistence of such founder effects are poorly understood, mainly because studies looking at the fine‐scale initial temporal dynamics of the genetic signature of a range expansion are rare. 2. Using microsatellite markers, we performed a detailed spatiotemporal genetic analysis of the range expanding damselfly Coenagrion scitulum (Rambur) along a coastal axis during the first years after colonisation. 3. A decrease was in (private) allelic richness when going northwards along the coastline, which is consistent with a scenario of cumulative founder events. In spite of the spatiotemporal dynamics in the observation records of the species along the coastline, the spatial genetic data indicated a major contribution from the broad expansion front during the colonisation of the coastline rather than a stepping‐stone colonisation process. 4. The fine‐scale temporal dynamics of the range expansion indicated the absence of persistent founder effects and instead showed considerable temporal instability in genetic indices at the more northern edge populations. This may be explained by genetic immigration and admixture from the broad expansion front in this active disperser. 相似文献
98.
SEVERAL characters involved in sexual dimorphism or male reproductive performance are influenced by genetic factors that are linked with the histocompatibility-2 (H-2) system of the mouse. These factors influence sperm cell production and function1–4 interstrain differences in relative weights of vesicular gland and testis4,5, immune response to the male-specific histocompatibility antigen6,7 and an androgen-dependent allotypic serum protein designated Slp8. Our finding of an H-2 linked gene influencing the size of such male hormone-dependent organs, as is the vesicular gland and testis, suggested that the amount of testosterone in plasma may be influenced by an H-2 linked gene. Whereas the genetic control of some hormonally determined traits is considered to be polygenic9,10, other data indicate some endocrine variation is due to allelic substitution at a single locus or very few loci11–14. These genes in the mouse genome have not yet been located. 相似文献
99.
100.
GUY M. L. PERRY TIM L. KING JR
ME ST.‐CYR MANON VALCOURT LOUIS BERNATCHEZ 《Molecular ecology resources》2005,5(2):346-351
The brook charr (Salvelinus fontinalis; Osteichthyes: Salmonidae) is a phenotypically diverse fish species inhabiting much of North America. But relatively few genetic diagnostic resources are available for this fish species. We isolated 41 microsatellites from S. fontinalis polymorphic in one or more species of salmonid fish. Thirty‐seven were polymorphic in brook charr, 15 in the congener Arctic charr (Salvelinus alpinus) and 14 in the lake charr (Salvelinus namaycush). Polymorphism was also relatively high in Oncorhynchus, where 21 loci were polymorphic in rainbow trout (Oncorhynchus mykiss) and 16 in cutthroat trout (Oncorhynchus clarkii) but only seven and four microsatellite loci were polymorphic in the more distantly related lake whitefish (Coregonus clupeaformis) and Atlantic salmon (Salmo salar), respectively. One duplicated locus (Sfo228Lav) was polymorphic at both duplicates in S. fontinalis. 相似文献