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71.
AbstractPharmacophore modeling and atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) have been developed on N-acylglycino- and hippurohydroxamic acid derivatives, which are known potential inhibitors of urease. This is followed by virtual screening and ADMET (absorption, distribution, metabolism, excretion and toxicity) studies on a large library of known drugs in order to get lead molecules as Helicobacter pylori urease inhibitors. A suitable three-featured pharmacophore model comprising one H-bond acceptor and two H-bond donor features (ADD.10) has been found to be the best QSAR model. An external library of compounds (~3000 molecules), pre-filtered using Lipinski’s rule of five, has been further screened using the pharmacophore model ADD.10. By analyzing the fitness of the hits with respect to the pharmacophore model and their binding interaction inside the urease active site, four molecules have been predicted to be extremely good urease inhibitors. Two of these have significant potential and should be taken up for further drug-designing process. 相似文献
72.
Joshi Deepmala Mittal Deepak Sadhana Srivastav Shukla Sangeeta Srivastav Ajai Kumar Srivastav Sunil Kumar 《Journal of trace elements in medicine and biology》2013,27(3):249-256
The present study was undertaken to establish mode of action, comparative therapeutic efficacy and safety evaluation of dithiothreitol (DTT) supplemented with Zn and Se against dimethylmercury in rats. Adult male albino rats of Sprague-Dawley strain (150 ± 10 g, n = 6 per group) were exposed a bolus dose of dimethylmercury (10 mg/kg, p.o.) for once only followed by DTT (15.4 mg/kg, i.p.) along with the combination of antioxidants Zn and Se (2 mmol/kg and 0.5 mg/kg, p.o.) after 72 h of toxicant administration for three days. The results showed a significant (P ≤ 0.05) increase in the activities of AST, ALT, alkaline phosphatase, lactate dehydrogenase, in serum after toxicant administration. This was accompanied by histopathological observations. A significant rise was observed in lipid peroxidation level and mercury ion concentration however reduced glutathione content decreased in liver, kidney and brain. A significant (P ≤ 0.05) decrease in the activity of acetyl cholinesterase was also seen in different regions of brain. Combined treatment of DTT along with Zn and Se significantly (P ≤ 0.05) recouped the alterations in the enzymatic activities of serum and reversed the tissue biochemical and histopathological changes of liver, kidney and brain. Our results demonstrate that combined treatment of thiol chelator (DTT) along with antioxidants (Zn and Se) plays an important role against dimethylmercury induced tissue damage and hepatic, nephro and neurotoxicity. 相似文献
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Pramod Kumar Yadav Gurmit Singh Budhayash Gautam Satendra Singh Madhu Yadav Upasana Srivastav Brijendra Singh 《Bioinformation》2013,9(3):158-164
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as a nosocomial pathogen to the
community which commonly causes skin and soft-tissue infections (SSTIs). This strain (MW2) has now become resistant to the
most of the beta-lactam antibiotics; therefore it is the urgent need to identify the novel drug targets. Recently fructose 1,6
biphosphate aldolase-II (FBA) has been identified as potential drug target in CA-MRSA. The FBA catalyses the retro-ketolic
cleavage of fructose-1,6-bisphosphate (FBP) to yield dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P)
in glycolytic pathway. In the present research work the 3D structure of FBA was predicted using the homology modeling method
followed by validation. The molecular dynamics simulation (MDS) of the predicted model was carried out using the 2000 ps time
scale and 1000000 steps. The MDS results suggest that the modeled structure is stable. The predicted model of FBA was used for
virtual screening against the NCI diversity subset-II ligand databases which contain 1364 compounds. Based on the docking energy
scores, it was found that top four ligands i.e. ZINC01690699, ZINC13154304, ZINC29590257 and ZINC29590259 were having lower
energy scores which reveal higher binding affinity towards the active site of FBA. These ligands might act as potent inhibitors for
the FBA so that the menace of antimicrobial resistance in CA-MRSA can be conquered. However, pharmacological studies are
required to confirm the inhibitory activity of these ligands against the FBA in CA-MRSA. 相似文献
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76.
Shekhar Mallick Navin Kumar Sarita Sinha Arvind Kumar Dubey Rudra Deo Tripathi Vivek Srivastav 《Physiology and Molecular Biology of Plants》2014,20(4):435-447
The study investigated the reduction in metalloid uptake at equimolar concentrations (~53.3 μM) of As(III) and As(V) in contrasting pair of rice seedlings by pretreating with H2O2 (1.0 μM) and SA (1.0 mM). Results obtained from the contrasting pair (arsenic tolerant vs. sensitive) of rice seedlings (cv. Pant Dhan 11 and MTU 7029, respectively) shows that pretreatment of H2O2 and H2O2 + SA reduces As(V) uptake significantly in both the cultivars, while no reduction in the As(III) uptake. The higher growth inhibition, higher H2O2 and TBARS content in sensitive cultivar against As(III) and As(V) treatments along with higher As accumulation (~1.2 mg g−1 dw) than in cv. P11, unravels the fundamental difference in the response between the sensitive and tolerant cultivar. In the H2O2 pretreated plants, the translocation of As increased in tolerant cultivar against AsIII, whereas, it decreased in sensitive cultivar both against AsIII and AsV. In both the cultivars translocation of Mn increased in the H2O2 pretreated plants against As(III), whereas, the translocation of Cu increased against As(V). In tolerant cultivar the translocation of Fe increased against As(V) with H2O2 pretreatment whereas, it decreased in the sensitive cultivar. In both the cultivars, Zn translocation increased against As(III) and decreased against As(V). The higher level of H2O2 and SOD (EC 1.15.1.1) activity in sensitive cultivar whereas, higher, APX (EC 1.11.1.11), GR (EC 1.6.4.2) and GST (EC 1.6.4.2) activity in tolerant cultivar, also demonstrated the differential anti-oxidative defence responses between the contrasting rice cultivars.
Electronic supplementary material
The online version of this article (doi:10.1007/s12298-014-0255-1) contains supplementary material, which is available to authorized users. 相似文献77.
78.
The present report deals with the occurrence of calcitonin cells (C cells) and cysts in the parathyroid IV of Suncus murinus. Histological preparations of the thyro-parathyroid complex reveal that (i) the parathyroid IV exhibits C cells either solitarily or in small groups (compact or follicular arrangement); (ii) the parathyroid IV also exhibits cysts (similar to those of the thyroid), the lining of these may contain either few C cells or it may be a continuous lining of C cells; (iii) the lumina of these cysts are filled with debris and desquamated cells with pycnotic nuclei, and (iv) sometimes few C cells are encountered hanging from the epithelial lining inside the lumen of the cyst. 相似文献
79.
Srivastav RK Schwede S Klaus M Schwermann J Gaestel M Niedenthal R 《The Biochemical journal》2011,438(3):495-503
Protein-protein interactions are essential for almost all cellular processes, hence understanding these processes mainly depends on the identification and characterization of the relevant protein-protein interactions. In the present paper, we introduce the concept of TRS (trans-SUMOylation), a new method developed to identify and verify protein-protein interactions in mammalian cells in vivo. TRS utilizes Ubc9-fusion proteins that trans-SUMOylate co-expressed interacting proteins. Using TRS, we analysed interactions of 65 protein pairs co-expressed in HEK (human embryonic kidney)-293 cells. We identified seven new and confirmed 16 known protein interactions, which were determined via endogenous SUMOylation sites of the binding partners or by using SUMOylation-site tags respectively. Four of the new protein interactions were confirmed by GST (glutathione transferase) pull-down and the p38α-Edr2 interaction was verified by co-localization analysis. Functionally, this p38α-Edr2 interaction could possibly be involved in the recruitment of p38α to the polycomb chromatin-remodelling complex to phosphorylate Bmi1. We also used TRS to characterize protein-interaction domains of the protein kinase pairs p38α-MK2 [MK is MAPK (mitogen-activated protein kinase)-activated protein kinase] and ERK3 (extracellular-signal-regulated kinase 3)-MK5 and of the p38α-p53 complex. The ability of TRS to monitor protein interactions in mammalian cells in vivo at levels similar to endogenous expression makes it an excellent new tool that can help in defining the protein interactome of mammalian cells. 相似文献
80.