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41.
Arun P. Chandrasekharappa Sangamesh E. Badiger Pramod K. Dubey Sunil K. Panigrahi Sekhar Reddy V.V.V. Manukonda 《Bioorganic & medicinal chemistry letters》2013,23(9):2579-2584
A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7 μM. Structure–activity relationship were explained with the help of molecular modeling approach. 相似文献
42.
Imran Ahmad Jay Prakash Thakur Debabrata Chanda Dharmendra Saikia Feroz Khan Shivani Dixit Amit Kumar Rituraj Konwar Arvind Singh Negi Atul Gupta 《Bioorganic & medicinal chemistry letters》2013,23(5):1322-1325
Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv strain. Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3.5 and 7.5 μg-mL?1. In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non-cancerous human epithelial kidney cell line (HEK-293) showed that most active compound 25a was approximately 2.85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective. 相似文献
43.
Pramod Kumar Singh Ramendra Singh Shivani Singh 《Physiology and Molecular Biology of Plants》2013,19(1):53-59
Plant growth and development are greatly affected due to changes in environmental conditions and become a serious challenge to scientific people. Therefore, present study was conducted to determine the role of secondary metabolites on the growth and development of maize under abiotic stress conditions. Cinnamic acid (CA) is one of the basic phenylpropanoid with antioxidant activity, produced by plants in response to stressful conditions. Response of maize seeds to the presoaking treatment with 0.5 mM CA was studied under different concentrations of NaCl stress. Exogenous CA increased growth characteristics in saline and non-saline conditions, while effects of CA were more significant under saline conditions in comparison to non-saline conditions in maize plants. CA also reduced oxidative damage through the induction of ROS scavenging enzymes such as supperoxide dismutase (SOD) (EC 1.15.1.1), peroxidase (POD) (EC 1.11.1.7), while the activity of enzyme catalase (CAT) (EC 1.11.1.6) was decreased. The content of malondialdehyde (MDA) was reduced significantly in maize leaf under CA treatment. Changes in protein banding patterns in the maize leaves showed a wide variation in response to NaCl-stress, while in the presence of CA salt-induced expression of polypeptides was reduced significantly. Present study clearly reports the alleviative effects of CA in response to salinity stress on growth, metabolic activity and changes in protein profile of 21 days old maize plants. 相似文献
44.
Sameena Khan Ankur Garg Arvind Sharma Noelia Camacho Daria Picchioni Adéla?de Saint-Léger Lluís Ribas de Pouplana Manickam Yogavel Amit Sharma 《PloS one》2013,8(6)
Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in complex with L-tryptophan. Confocal microscopy-based localization data suggest cytoplasmic residency of this protein. Pf-WRS has an unusual N-terminal extension of AlaX-like domain (AXD) along with linker regions which together seem vital for enzymatic activity and tRNA binding. Pf-WRS is not proteolytically processed in the parasites and therefore AXD likely provides tRNA binding capability rather than editing activity. The N-terminal domain containing AXD and linker region is monomeric and would result in an unusual overall architecture for Pf-WRS where the dimeric catalytic domains have monomeric AXDs on either side. Our PDB-wide comparative analyses of 47 WRS crystal structures also provide new mechanistic insights into this enzyme family in context conserved KMSKS loop conformations. 相似文献
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46.
Pramod Sukumaran Max L?nnfors Otto L?ngvik Ilari Pulli Kid T?rnquist J. Peter Slotte 《PloS one》2013,8(4)
Ceramides are potent bioactive molecules in cells. However, they are very hydrophobic molecules, and difficult to deliver efficiently to cells. We have made fluid bilayers from a short-chain D-erythro-ceramide (C6-Cer) and cholesteryl phosphocholine (CholPC), and have used this as a formulation to deliver ceramide to cells. C6-Cer complexed with CholPC led to much larger biological effects in cultured cells (rat thyroid FRTL-5 and human HeLa cells in culture) compared to C6-Cer dissolved in dimethyl sulfoxide (DMSO). Inhibition of cell proliferation and induction of apoptosis was significantly more efficient by C6-Cer/CholPC compared to C6-Cer dissolved in DMSO. C6-Cer/CholPC also permeated cell membranes and caused mitochondrial Ca2+ influx more efficiently than C6-Cer in DMSO. Even though CholPC was taken up by cells to some extent (from C6-Cer/CholPC bilayers), and was partially hydrolyzed to free cholesterol (about 9%), none of the antiproliferative effects were due to CholPC or excess cholesterol. The ceramide effect was not limited to D-erythro-C6-Cer, since L-erythro-C6-Cer and D-erythro-C6-dihydroCer also inhibited cell priolifereation and affected Ca2+ homeostasis. We conclude that C6-Cer complexed to CholPC increased the bioavailability of the short-chain ceramide for cells, and potentiated its effects in comparison to solvent-dissolved C6-Cer. This new ceramide formulation appears to be superior to previous solvent delivery approaches, and may even be useful with longer-chain ceramides. 相似文献
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48.
Ahmed Aljameeli Arvind Thakkar Shibu Thomas Vijaybasker Lakshmikanthan Kenneth A. Iczkowski Girish V. Shah 《PloS one》2016,11(3)
The role of neuroendocrine peptide calcitonin (CT) and its receptor (CTR) in epithelial cancer progression is an emerging concept with great clinical potential. Expression of CT and CTR is frequently elevated in prostate cancers (PCs) and activation of CT–CTR axis in non-invasive PC cells induces an invasive phenotype. Here we show by yeast-two hybrid screens that CTR associates with the tight junction protein Zonula Occludens-1 (ZO-1) via the interaction between the type 1 PDZ motif at the carboxy-terminus of CTR and the PDZ3 domain of ZO-1. Mutation of either the CTR C-PDZ-binding motif or the ZO-1-PDZ3 domain did not affect binding of CTR with its ligand or G-protein-mediated signaling but abrogated destabilizing actions of CT on tight junctions and formation of distant metastases by orthotopically implanted PC cells in nude mice, indicating that these PDZ domain interactions were pathologically relevant. Further, we observed CTR-ZO-1 interactions in PC specimens by proximity ligation immunohistochemistry, and identified that the number of interactions in metastatic PC specimens was several-fold larger than in non-metastatic PC. Our results for the first time demonstrate a mechanism by which PDZ-mediated interaction between CTR and ZO1 is required for CT-stimulated metastasis of prostate cancer. Since many receptors contain PDZ-binding motifs, this would suggest that PDZ-binding motif-adaptor protein interactions constitute a common mechanism for cancer metastasis. 相似文献
49.