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991.
An efficient biocatalytic method has been developed for the conversion of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester (1) into the corresponding amide (5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid, 1-(1,1-dimethylethyl)ester (2), which is a critical intermediate in the synthesis of the dipeptidyl peptidase IV (DPP4) inhibitor Saxagliptin (3). Candida antartica lipase B mediates ammonolysis of the ester with ammonium carbamate as ammonia donor to yield up to 71% of the amide. The inclusion of Ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol byproducts, respectively, increases the yield to 98%, thereby offering an efficient and practical alternative to chemical routes which yield 57-64%. 相似文献
992.
Karthikeyan MS Prasad DJ Poojary B Subrahmanya Bhat K Holla BS Kumari NS 《Bioorganic & medicinal chemistry》2006,14(22):7482-7489
A series of 2,4-dichloro-5-fluorophenyl bearing Mannich base (4 and 5) was prepared from triazole Schiff bases (3) by aminomethylation with formaldehyde and secondary/substituted primary amines. All newly synthesized compounds were screened for their antimicrobial activity. Compounds 3c, 4c, 4e and 4f exhibited promising antibacterial and compounds 3c, 5c, 5e and 5f showed good antifungal activity. 相似文献
993.
Singh SK Vobbalareddy S Kalleda SR Casturi SR Datla SR Mamidi RN Mullangi R Ramanujam R Yeleswarapu KR Iqbal J 《Bioorganic & medicinal chemistry》2006,14(24):8626-8634
Synthesis of prodrugs of orally active COX-2 inhibitor 3 involving sulfamoyl (SO2NH2) and hydroxymethyl (CH2OH) groups, and their biological evaluation are described. Of these prodrugs, the N-propionyl sulfonamide sodium 3k was found to be much superior to the parent compound 3 and other marketed COX-2 inhibitors in carrageenan induced rat paw edema model of inflammation due to highly elevated drug levels in systemic circulation. This prodrug has a potential both for oral as well as parenteral administration due to impressive analgesic activity, antipyretic potency, and extraordinary water solubility. 相似文献
994.
Verma AK Bansal S Singh J Tiwari RK Kasi Sankar V Tandon V Chandra R 《Bioorganic & medicinal chemistry》2006,14(19):6733-6736
Three haloderivatives of noscapine 2-4 were synthesized chemoselectively and their in vitro cytotoxicity was assessed by MTT assay on U-87 human glioblastoma cell lines. At 50 microM concentration after 72 h, 9-chloronoscapine 2, 9-bromonoscapine 3 (EM011), and 9-iodonoscapine 4 killed 87.8%, 51.2%, and 56.8% cells, respectively, however noscapine kills only 40% of the cells; revealing 9-chloronoscapine as a potential cytotoxic agent than noscapine and 9-bromonoscapine (EM011). At low concentration (1 microM) 9-bromonoscapine (46.7%) and 9-chloronoscapine (45.7%) did not show any significant difference. 相似文献
995.
Chaudhary P Kumar R Verma AK Singh D Yadav V Chhillar AK Sharma GL Chandra R 《Bioorganic & medicinal chemistry》2006,14(6):1819-1826
A series of substituted piperazine derivatives have been synthesized and tested for antimicrobial activity. The antibacterial activity was tested against Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652), and antifungal activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. All synthesized compounds showed significant activity against bacterial strains but were found to be less active against tested fungi. In vitro toxicity tests demonstrated that compounds 4d and 6a showed very less toxicity against human erythrocytes. 相似文献
996.
Polarity and temporality of high-resolution y-chromosome distributions in India identify both indigenous and exogenous expansions and reveal minor genetic influence of Central Asian pastoralists 总被引:5,自引:0,他引:5
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Sengupta S Zhivotovsky LA King R Mehdi SQ Edmonds CA Chow CE Lin AA Mitra M Sil SK Ramesh A Usha Rani MV Thakur CM Cavalli-Sforza LL Majumder PP Underhill PA 《American journal of human genetics》2006,78(2):202-221
Although considerable cultural impact on social hierarchy and language in South Asia is attributable to the arrival of nomadic Central Asian pastoralists, genetic data (mitochondrial and Y chromosomal) have yielded dramatically conflicting inferences on the genetic origins of tribes and castes of South Asia. We sought to resolve this conflict, using high-resolution data on 69 informative Y-chromosome binary markers and 10 microsatellite markers from a large set of geographically, socially, and linguistically representative ethnic groups of South Asia. We found that the influence of Central Asia on the pre-existing gene pool was minor. The ages of accumulated microsatellite variation in the majority of Indian haplogroups exceed 10,000-15,000 years, which attests to the antiquity of regional differentiation. Therefore, our data do not support models that invoke a pronounced recent genetic input from Central Asia to explain the observed genetic variation in South Asia. R1a1 and R2 haplogroups indicate demographic complexity that is inconsistent with a recent single history. Associated microsatellite analyses of the high-frequency R1a1 haplogroup chromosomes indicate independent recent histories of the Indus Valley and the peninsular Indian region. Our data are also more consistent with a peninsular origin of Dravidian speakers than a source with proximity to the Indus and with significant genetic input resulting from demic diffusion associated with agriculture. Our results underscore the importance of marker ascertainment for distinguishing phylogenetic terminal branches from basal nodes when attributing ancestral composition and temporality to either indigenous or exogenous sources. Our reappraisal indicates that pre-Holocene and Holocene-era--not Indo-European--expansions have shaped the distinctive South Asian Y-chromosome landscape. 相似文献
997.
Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis 总被引:6,自引:0,他引:6
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Han CS Xie G Challacombe JF Altherr MR Bhotika SS Brown N Bruce D Campbell CS Campbell ML Chen J Chertkov O Cleland C Dimitrijevic M Doggett NA Fawcett JJ Glavina T Goodwin LA Green LD Hill KK Hitchcock P Jackson PJ Keim P Kewalramani AR Longmire J Lucas S Malfatti S McMurry K Meincke LJ Misra M Moseman BL Mundt M Munk AC Okinaka RT Parson-Quintana B Reilly LP Richardson P Robinson DL Rubin E Saunders E Tapia R Tesmer JG Thayer N Thompson LS Tice H Ticknor LO Wills PL Brettin TS Gilna P 《Journal of bacteriology》2006,188(9):3382-3390
Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms. 相似文献
998.
Rodriguez-Agudo D Ren S Hylemon PB Montañez R Redford K Natarajan R Medina MA Gil G Pandak WM 《Journal of lipid research》2006,47(6):1168-1175
Human StarD5 belongs to the StarD4 subfamily of START (for steroidogenic acute regulatory lipid transfer) domain proteins. We previously reported that StarD5 is located in the cytosolic fraction of human liver and binds cholesterol and 25-hydroxycholesterol. After overexpression of the gene encoding StarD5 in primary rat hepatocytes, free cholesterol accumulated in intracellular membranes. These findings suggested StarD5 to be a directional cytosolic sterol transporter. The objective of this study was to determine the localization of StarD5 in human liver. Western blot analysis confirmed StarD5's presence in the liver but not in human hepatocytes. Immunohistochemistry studies showed StarD5 localized within sinusoidal lining cells in the human liver and colocalized with CD68, a marker for Kupffer cells. Western blot analyses identified the presence of StarD5 in monocytes and macrophages as well as mast cells, basophils, and promyelocytic cells, but not in human hepatocytes, endothelial cells, fibroblasts, osteocytes, astrocytes, or brain tissue. Cell fractionation and immunocytochemistry studies on THP-1 macrophages localized StarD5 to the cytosol and supported an association with the Golgi. The presence of this cholesterol/25-hydroxycholesterol-binding protein in cells related to inflammatory processes provides new clues to the role of this protein in free sterol transport in the cells and in lipid-mediated atherogenesis. 相似文献
999.
1000.
Geetha T Zheng C Unroe B Sycheva M Kluess H Babu JR 《Biochemical and biophysical research communications》2012,421(2):286-290
Specific binding of nerve growth factor (NGF) to p75 neurotrophin receptor (p75(NTR)) leads to p75(NTR) polyubiquitination and its subsequent interaction with TRAF6 resulting in neuronal cell survival. However, when the binding of NGF to p75(NTR) was blocked with p75 antiserum, p75(NTR) polyubiquitination and neuronal cell survival were impaired. Results showed that tyrosine phosphorylation of p75(NTR) increased the polyubiquitination of p75(NTR) and contributed to the observed apparent neuroprotective effects. Similar to p75(NTR) polyubiquitination, interaction of TRAF6 with p75(NTR) was NGF/tyrosine phosphorylation dependent suggesting that TRAF6 might function as an E3 ubiquitin ligase. In sum, the results show that specific binding of NGF to p75(NTR) mediates neuronal cell survival. 相似文献