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81.
Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration
Kondo T Nekado T Sugimoto I Ochi K Takai S Kinoshita A Tajima Y Yamamoto S Kawabata K Nakai H Toda M 《Bioorganic & medicinal chemistry》2007,15(7):2631-2650
A series of 5beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented. 相似文献
82.
Ali HI Tomita K Akaho E Kambara H Miura S Hayakawa H Ashida N Kawashima Y Yamagishi T Ikeya H Yoneda F Nagamatsu T 《Bioorganic & medicinal chemistry》2007,15(1):242-256
Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK. 相似文献
83.
Jimbo M Usui R Sakai R Muramoto K Kamiya H 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,147(2):164-171
Three L-rhamnose-binding egg lectins, TBL1, TBL2 and TBL3, were isolated from the eggs of the Far East dace Tribolodon brandti by a combination of affinity chromatography on L-rhamnose-Sepharose 6B gel and reversed-phase HPLC. L-rhamnose is a common inhibitor of the purified lectins and strongly inhibited the hemagglutinating activity of TBL2 and TBL3, but less weakly that of TBL1. L-arabinose, which has the same hydroxyl group orientation at C2 and C4 as L-rhamnose, and D-galactose showed no inhibitory activity against TBL1 but showed weak inhibitory activity against TBL2 and TBL3. The open reading frames of the cDNAs of TBL1, TBL2 and TBL3 encoded for mature proteins of 207, 189, and 293 amino acid residues, respectively. A BLAST homology search showed that the TBLs have about 40% homology to the carbohydrate recognition domains of rhamnose-binding lectins in salmonid eggs. The tandem repeated domains present in TBL1, TBL2 and TBL3 were two, two and three, respectively. TBL2 was exclusively expressed in ovary, while TBL1 and TBL3 were expressed mainly in ovary and weakly in various tissues including gill, heart, kidney, liver, spleen and testis. 相似文献
84.
Li LH Zhou XN Du ZW Wang XZ Wang LB Jiang JY Yoshikawa H Steinmann P Utzinger J Wu Z Chen JX Chen SH Zhang L 《Parasitology international》2007,56(4):281-286
The purpose of this study was to improve our understanding of the molecular epidemiology of human Blastocystis, focusing on 239 randomly selected individuals in a single village in Yunnan province, China. Emphasis was placed on the relative frequency of different Blastocystis subtypes and underlying risk factors. We used a cross-sectional study design, by employing a pre-tested questionnaire to obtain demographic data and behavioural risk factors, and collected faecal samples for culture and subsequent identification of Blastocystis. DNA was extracted from Blastocystis isolates and the subtypes were identified using 7 subtype-specific sequenced-tagged site (STS) primers. Overall, 78 faecal samples were Blastocystis culture-positive (32.6%, 95% confidence interval: 26.7–38.6%). The majority (n = 73, 93.6%) were single infections with one of the known subtypes, whereas 2 isolates consisted of 2 concurrent subtypes. The remaining 3 isolates could not be identified with the currently known STS primers. Risk factors for a Blastocystis infection were drinking unboiled water, consumption of raw water plants and pig ownership. The consumption of raw water plants was positively associated with subtype 1 infections, and drinking unboiled water with subtype 3 infections. In conclusion, human Blastocystis was common in this village in southwest China, and different subtypes were associated with distinct transmission routes or sources of infection, and hence Blastocystis subtypes might be linked to specific environmental compartments. 相似文献
85.
Iguchi A Ebisu A Nagata S Saitou Y Yoshikawa H Iwatani S Kimata I 《Parasitology international》2007,56(2):107-112
Most Blastocystis hominis isolates from humans are believed to be potentially zoonotic. This is because B. hominis isolates found in a variety of other host species have been found to have identical or relatively similar genotypes to those found in human isolates. However, the transmission of human B. hominis isolates to other animals has not been confirmed experimentally. In this study, the infectivity associated with several unique human Blastocystis genotypes (subtypes 2, 3, 4 and 7) was therefore investigated by infecting chickens and rats with two isolates of each subtype experimentally. The results showed that one isolate of subtype 4 and one isolate of subtype 7 was capable of infecting both chickens and rats, while two isolates of subtype 2, another isolate of subtype 4, and another isolate of subtype 7 could only infect chickens. Conversely, two isolates of subtype 3 failed to infect either of the animals. These results confirmed that several genotypes from human isolates could infect chickens and/or rats, indicating that chickens and rats are suitable experimental animal models for studying the zoonotic potential of human Blastocystis isolates. 相似文献
86.
Stensvold CR Suresh GK Tan KS Thompson RC Traub RJ Viscogliosi E Yoshikawa H Clark CG 《Trends in parasitology》2007,23(3):93-96
Blastocystis is a ubiquitous enteric protistan parasite that has extensive genetic diversity and infects humans and many other animals. Distinct molecular methodologies developed to detect variation and obtain information about transmission patterns and clinical importance have resulted in a confusing array of terminologies for the identification and designation of Blastocystis subtypes. In this article, we propose a standardization of Blastocystis terminology to improve communication and correlate research results. Based primarily on published small-subunit ribosomal RNA gene analyses, we propose that all mammalian and avian isolates should be designated Blastocystis sp. and assigned to one of nine subtypes. 相似文献
87.
Yuri Ishii Naoki Akasaka Itsuko Goda Hisao Sakoda Shinsuke Fujiwara 《Applied and environmental microbiology》2015,81(7):2265-2273
Acetoin in vinegar is an attractant to fruit flies when combined with acetic acid. To make vinegar more effective in attracting fruit flies with increased acetoin production, Komagataeibacter europaeus KGMA0119 was modified by specific gene disruption of the acetohydroxyacid isomeroreductase gene (ilvC). A previously constructed mutant lacking the putative ligand-sensing region in the leucine-responsive regulatory protein (KeLrp, encoded by Kelrp) was also used. The ilvC and Kelrp disruptants (KGMA5511 and KGMA7203, respectively) produced greater amounts of acetoin (KGMA5511, 0.11%; KGMA7203, 0.13%) than the wild-type strain KGMA0119 (0.069%). KGMA7203 produced a trace amount of isobutyric acid (0.007%), but the other strains did not. These strains produced approximately equal amounts of acetic acid (0.7%). The efficiency of fruit fly attraction was investigated with cultured Drosophila melanogaster. D. melanogaster flies (approximately 1,500) were released inside a cage (2.5 m by 2.5 m by 1.5 m) and were trapped with a device containing vinegar and a sticky sheet. The flies trapped on the sticky sheet were counted. The cell-free supernatant from KGMA7203 culture captured significantly more flies (19.36 to 36.96% of released flies) than did KGMA0119 (3.25 to 11.40%) and KGMA5511 (6.87 to 21.50%) cultures. Contrastingly, a 0.7% acetic acid solution containing acetoin (0.13%) and isobutyric acid (0.007%), which mimicked the KGMA7203 supernatant, captured significantly fewer flies (0.88 to 4.57%). Furthermore, the KGMA0119 supernatant with additional acetoin (0.13%) and isobutyric acid (0.007%) captured slightly more flies than the original KGMA0119 supernatant but fewer than the KGMA7203 supernatant, suggesting that the synergistic effects of acetic acid, acetoin, isobutyric acid, and unidentified metabolites achieved the efficient fly trapping of the KGMA7203 supernatant. 相似文献
88.
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90.
Saito T Obitsu T Kondo T Matsui T Nagao Y Kusumi K Matsumura N Ueno S Kishi A Katsumata S Kagamiishi Y Nakai H Toda M 《Bioorganic & medicinal chemistry》2011,19(18):5432-5445
To identify an orally active corticotropin-releasing factor 1 receptor antagonist, a series of 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives were designed, synthesized and evaluated. An in vitro study followed by in vivo and pharmacokinetic studies of these heterotricyclic compounds led us to the discovery of an orally active CRF1 receptor antagonist. The results of a structure-activity relationship study are presented. 相似文献