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111.
William Horton Abha Sood Swarada Peerannawar Nandor Kugyela Aditya Kulkarni Rekha Tulsan Chris D. Tran Jessica Soule Harry LeVine Béla Török Marianna Török 《Bioorganic & medicinal chemistry letters》2017,27(2):232-236
The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer’s disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies. 相似文献
112.
A comparative study of predation of three aquatic heteropteran bugs on Culex quinquefasciatus larvae
The aquatic bugs Anisops bouvieri Kirkaldy 1704 (Heteroptera: Notonectidae), Diplonychus (=Sphaerodema) rusticus Fabricius 1781, and Diplonychus annulatus Fabricius 1781 (Heteroptera: Belostomatidae) are common members of the freshwater insect communities of the East Calcutta
Wetlands along the eastern fringe of Kolkata, India. These insects are established predators of dipteran larvae and other
organisms. A comparative account of their predatory efficiency was made using larvae of Culex quinquefasciatus Say 1823 in the laboratory. It was revealed that a single adult of A. bouvieri could consume 28–34 fourth-instar mosquito larvae per day, D. rusticus 11–87 fourth-instar mosquito larvae per day, and D. annulatus 33–122 fourth-instar mosquito larvae per day, depending upon the prey and predator densities. The mean predation rate of
A. bouvieri and D. annulatus remained stable over a 6-day feeding period but varied for D. rusticus. The predatory impact (PI) values were 14.77–17.31, 46.9–55.73, and 61.74–72.72 larvae/day for A. bouvieri, D. rusticus, and D. annulatus, respectively. Compared to these, the clearance rate (CR) value range was 9.06–13.25 for A. bouvieri, 13.64–15.99 for D. rusticus, and 13.50–16.52 larvae l/day/predator for D. annulatus. The values of mutual interference, “m,” remained 0.06–0.78 for A. bouvieri, 0.003–0.25 for D. rusticus, and 0.09–0.27 for D. annulatus, and did not vary between the days. The difference in predatory efficiency, CR, and PI values varied significantly among
the three predators, indicating the possible difference in the function as predators occupying the same guild. It can be assumed
that these predators play an important role in larval population regulation of mosquitoes and thereby impart an effect on
species composition and interactions in the aquatic insect communities of the wetlands and other similar habitats where they
occur. 相似文献
113.
Administration of IκB‐kinase inhibitor PS1145 enhances apoptosis in DMBA‐induced tumor in male Wistar rats
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114.
The draft genome sequence (4.84 Mb) of Cecembia lonarensis strain LW9T, isolated from a water sample (4.5-m depth) from Lonar Lake, a meteorite-created haloalkaline lake in India, is reported. The enzymes produced by these microorganisms need to be stable under alkaline conditions prevailing in its habitat. Such enzymes would be of immense importance for enzymatic processes operating at high pH. 相似文献
115.
AS Vaidya B Karumudi E Mendonca A Madriaga H Abdelkarim RB van Breemen PA Petukhov 《Bioorganic & medicinal chemistry letters》2012,22(15):5025-5030
The design, modeling, synthesis, biological evaluation of a novel series of photoreactive benzamide probes for class I HDAC isoforms is reported. The probes are potent and selective for HDAC1 and 2 and are efficient in crosslinking to HDAC2 as demonstrated by photolabeling experiments. The probes exhibit a time-dependent inhibition of class I HDACs. The inhibitory activities of the probes were influenced by the positioning of the aryl and alkyl azido groups necessary for photocrosslinking and attachment of the biotin tag. The probes inhibited the deacetylation of H4 in MDA-MB-231 cell line, indicating that they are cell permeable and target the nuclear HDACs. 相似文献
116.
Aditya Sudheer Vaidya Raghupathi Neelarapu Antonett Madriaga He Bai Emma Mendonca Hazem Abdelkarim Richard B. van Breemen Sylvie Y. Blond Pavel A. Petukhov 《Bioorganic & medicinal chemistry letters》2012,22(21):6621-6627
A novel series of HDAC8 inhibitors without a zinc-chelating hydroxamic acid moiety is reported. Photoaffinity labeling and molecular modeling studies suggest that these ligands are likely to bind in an ‘upside-down’ fashion in a secondary binding site proximal to the main catalytic site. The most potent ligand in the series exhibits an IC50 of 28 μM for HDAC8 and is found to inhibit the deacetylation of H4 but not α-tubulin in SH-SY5Y cell line. 相似文献
117.
OBJECTIVE: To devise an optimal cytology threshold for colposcopy referral in resource-limited settings. STUDY DESIGN: Four hundred seventy-two symptomatic women 20-60 years old were screened by both cytology and colposcopy. Onsite biopsy was taken if lesions grade 1 or above were detected on colposcopy. Women found to have cervical intraepithelial neoplasia (CIN) 2 and above lesions on histopathology were stratified according to their cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]+ threshold, low grade squamous intraepithelial lesion [LSIL]+ threshold, and high grade squamous intraepithelial lesion [HSIL]+ threshold). The comparative sensitivity, specificity and predictive values in each group were calculated, taking biopsy as the gold standard. RESULTS: The sensitivity of LSIL + cytology to detect CIN 2+ lesions was 91.5% (referral load, 30.7%). While the sensitivity of ASCUS+ cytology threshold was almost the same (92.3%), the referral load was much higher (42.2%). With HSIL+ cytology threshold, though the referral load was reduced substantially (21.9%), the sensitivity also decreased, to 81.5%. CONCLUSION: The results indicate that in order to achieve high sensitivity, the LSIL cytology threshold appears to be optimum for colposcopic referrals. 相似文献
118.
Aditya K. Sanki Julie Boucau Donald R. Ronning Steven J. Sucheck 《Glycoconjugate journal》2009,26(5):589-596
Antigen 85 (ag85) is a complex of acyltransferases (ag85A–C) known to play a role in the mycolation of the d-arabino-d-galactan (AG) component of the mycobacterial cell wall. In order to better understand the chemistry and substrate specificity
of ag85, a trehalose monomycolate mimic p-nitrophenyl 6-O-octanoyl-β-d-glucopyranoside (1) containing an octanoyl moiety in lieu of a mycolyl moiety was synthesized as an acyl donor. Arabinofuranoside acceptors, methyl α-d-arabinofuranoside (2), methyl β-d-arabinofuranoside (3), and methyl 2-O-β-d-arabinofuranosyl-α-d-arabinofuranoside (9) were synthesized to mimic the terminal saccharides found on the AG. The acyl transfer reaction between acyl donor 1 and acceptors 2, 3, and 9 in the presence of ag85C from Mycobacterium tuberculosis (M. tuberculosis) resulted in the formation of esters, methyl 2, 5-di-O-octanoyl-α-d-arabinofuranoside (10), methyl 5-O-octanoyl-β-d-arabinofuranoside (11), and methyl 2-O-(5-O-octanoyl-β-d-arabinofuranosyl)-5-O-octanoyl-α-d-arabinofuranoside (12) in 2 h, 2 h and 8 h, respectively. The initial velocities of the reactions were determined with a newly developed assay
for acyltransferases. As expected, the regioselectivity corresponds to mycolylation patterns found at the terminus of the
AG in M. tuberculosis. The study shows that d-arabinose-based derivatives are capable of acting as substrates for ag85C-mediated acyl-transfer and the acyl glycoside 1 can be used in lieu of TMM extracted from bacteria to study ag85-mediated acyl-transfer and inhibition leading to the better understanding of
the ag85 protein class.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
119.
The prevalence of drug-resistant strains of Mycobacterium tuberculosis (M. tb) emphasizes the need for new antitubercular drugs. An essential component of the drug discovery process is the development of tools to rapidly screen potential drug libraries against important biological targets. Similarly to well-documented M. tb targets, the antigen 85 (Ag85) enzymes are involved in the maintenance of the mycobacterial cell wall. The products synthesized by these mycolyltransferases are the cell wall components most responsible for the reduced permeability of drugs into the bacterial cell, thereby linking Ag85 activity directly with drug resistance. This article presents the development of a high-throughput colorimetric assay suitable for direct monitoring of the enzymatic activity. The assay uses a synthetic substrate containing three chemical moieties: an octanoyl fatty acid, β-d-glucose, and p-nitrophenyl. In the context of the assay, Ag85 catalyzes the removal of the fatty acid and releases p-nitrophenyl-β-d-glucoside. The glucoside is hydrolyzed by β-glucosidase to release the p-nitrophenolate chromophore. With this assay, the KM and kcat values of Ag85C were determined to be 0.047 ± 0.008 mM and 0.062 s−1, respectively. In addition, the assay exhibits a Z′ value of 0.81 ± 0.06, indicating its suitability for high-throughput screening applications and drug development. 相似文献
120.
Gohar Mazmanian Michael Kovshilovsky Debbie Yen Aditya Mohanty Sudipta Mohanty Alex Nee Robert M. Nissen 《Genesis (New York, N.Y. : 2000)》2010,48(1):20-30
Nodal‐signaling is required for specification of mesoderm, endoderm, establishing left–right asymmetry, and craniofacial development. Wdr68 is a WD40‐repeat domain‐containing protein recently shown to be required for endothelin‐1 (edn1) expression and subsequent lower jaw development. Previous reports detected the Wdr68 protein in multiprotein complexes containing mammalian members of the dual‐specificity tyrosine‐regulated kinase (dyrk) family. Here we describe the characterization of the zebrafish dyrk1b homolog. We report the detection of a physical interaction between Dyrk1b and Wdr68. We also found perturbations of nodal signaling in dyrk1b antisense morpholino knockdown (dyrk1b‐MO) animals. Specifically, we found reduced expression of lft1 and lft2 (lft1/2) during gastrulation and a near complete loss of the later asymmetric lft1/2 expression domains. Although wdr68‐MO animals did not display lft1/2 expression defects during gastrulation, they displayed a near complete loss of the later asymmetric lft1/2 expression domains. While expression of ndr1 was not substantially effected during gastrulation, ndr2 expression was moderately reduced in dyrk1b‐MO animals. Analysis of additional downstream components of the nodal signaling pathway in dyrk1b‐MO animals revealed modestly expanded expression of the dorsal axial mesoderm marker gsc while the pan‐mesodermal marker bik was largely unaffected. The endodermal markers cas and sox17 were also moderately reduced in dyrk1b‐MO animals. Notably, and similar to defects previously reported for wdr68 mutant animals, we also found reduced expression of the pharyngeal pouch marker edn1 in dyrk1b‐MO animals. Taken together, these data reveal a role for dyrk1b in endoderm formation and craniofacial patterning in the zebrafish. genesis 48:20–30, 2010. © 2009 Wiley‐Liss, Inc. 相似文献