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71.
Sudipta Hazra Subhalakshmi Ghosh Madhushree Das Sarma Smriti Sharma Mousumi Das Prakash Saudagar Vijay Kumar Prajapati Vikash Kumar Dubey Shyam Sundar Banasri Hazra 《Experimental parasitology》2013
World health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis-naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including Leishmania. Presently, we have investigated the antileishmanial effect of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo. Further, the safety profile of D17 was established by testing its toxicity against normal macrophage cells (IC50 ∼ 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 ∼ 7.2 μM) as compared to diospyrin (IC50 ∼ 12.6 μM) against Leishmania donovani promastigotes. Again, D17 was tested on L. donovani BHU1216 isolated from a sodium stibogluconate-unresponsive patient, and exhibited selective inhibition of the intracellular amastigotes (IC50 ∼ 0.18 μM). Also, treatment of infected BALB/c mice with D17 at 2 mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently, computational docking studies were undertaken on selected enzymes of trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non-competitive inhibition of the L. donovani ODC, but could not inhibit TryR. 相似文献
72.
Md. Golam Sharoar Md. Shahnawaz Md. Imamul Islam Vijay Sankar Ramasamy Song Yub Shin Il-Seon Park 《Archives of biochemistry and biophysics》2013
The aggregation of β-amyloid (Aβ) peptide from its monomeric to its fibrillar form importantly contributes to the development of Alzheimer’s disease. Here, we investigated the effects of Escherichia coli maltose binding protein (MBP), which has been previously used as a fusion protein, on Aβ42 fibrillization, in order to improve understanding of the self-assembly process and the cytotoxic mechanism of Aβ42. MBP, at a sub-stoichiometric ratio with respect to Aβ42, was found to have chaperone-like inhibitory effects on β-sheet fibril formation, due to the accumulation of Aβ42 aggregates by sequestration of active Aβ42 species as Aβ42-MBP complexes. Furthermore, MBP increased the lag time of Aβ42 polymerization, decreased the growth rate of fibril extension, and suppressed Aβ42 mediated toxicity in human neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active concentration of Aβ42 by sequestering it as Aβ42-MBP complex, and that this sequestration suppresses ongoing nucleation and retards the growth rate of Aβ42 species required for fibril formation. We speculate that inhibition of the growth rate of potent Aβ42 species by MBP suppresses Aβ42-mediated toxicity in SH-SY5Y cells. 相似文献
73.
Spores of Ganoderma applanatum were collected by gravity. The spore extract was prepared and its biochemical and immunological properties were examined. In isoelectric focusing, the extract had 10–12 bands with pl values between 3.5 to 6.0, the strongest being at 3.5, 3.75, 4.55 and 5.2. In crossedradioimmunoelectrophoresis using human atopic sera, the extract had two dominant and two minor allergens. In IgE immunoblots of sodium dodecylsulphate polyacrylamide gel electrophoresis, the extract showed reactivity at 82, 45, 33, 26, 16, 11 kDa MW, the strongest being at 45 kDa MW. These results indicate that G. applanatum contains a complex mixture of allergens. 相似文献
74.
Se-Ho Kim Benjamin Markovitz Richard Trovato Brett R. Murphy Harry Austin Adam J. Willardsen Vijay Baichwal Scott Morham Ashok Bajji 《Bioorganic & medicinal chemistry letters》2013,23(10):2888-2892
A new oxazole scaffold showing great promise in HIV-1 inhibition has been discovered by cell-based screening of an in-house library and scaffold modification. Follow-up SAR study focusing on the 5-aryl substituent of the oxazole core has identified 4k (EC50 = 0.42 μM, TI = 50) as a potent inhibitor. However, the analogues suffered from poor aqueous solubility. To address this issue, we have developed broadly applicable potential prodrugs of indazoles. Among them, N-acyloxymethyl analogue 11b displayed promising results (i.e., increased aqueous solubility and susceptibility to enzymatic hydrolysis). Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical and PK properties 相似文献
75.
Vijay M. Shahani Daniel P. Ball Allan V. Ramos Zhihua Li Paul A. Spagnuolo Sina Haftchenary Aaron D. Schimmer Suzanne Trudel Patrick T. Gunning 《Bioorganic & medicinal chemistry》2013,21(17):5618-5628
A focused library of hetero-trisubstituted purines was developed for improving the cell penetrating and biological efficacy of a series of anti-Stat3 protein inhibitors. From this SAR study, lead agent 22e was identified as being a promising inhibitor of MM tumour cells (IC50’s <5 μM). Surprisingly, biophysical and biochemical characterization proved that 22e was not a Stat3 inhibitor. Initial screening against the kinome, prompted by the purine scaffold’s history for targeting ATP binding pockets, suggests possible targeting of the JAK family kinases, as well for ABL1 (nonphosphorylated F317L) and AAK1. 相似文献
76.
Sharad Chandra Deepak Ameta Sudarshan Kumar Vijay Sudhanshu Kumar Dwivedi Ram Kirti Saran 《Indian pacing and electrophysiology journal》2013,13(2):84-87
Inferior vena caval thrombosis is an unusual complication of permanent pacemaker implantation. The clinical presentation due to thrombosis depends on the site of thrombus. We have described here a rare case of pacemaker lead associated thrombosis of inferior vena cava, its diagnostic work up and briefly reviewed the existing literature of this uncommon complication. 相似文献
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79.
Ming-Hsu Chen Prabhjot Kaur Bruce Dien Frederick Below Michael L. Vincent Vijay Singh 《World journal of microbiology & biotechnology》2013,29(8):1509-1515
Tropical maize is an alternative energy crop being considered as a feedstock for bioethanol production in the North Central and Midwest United States. Tropical maize is advantageous because it produces large amounts of soluble sugars in its stalks, creates a large amount of biomass, and requires lower inputs (e.g. nitrogen) than grain corn. Soluble sugars, including sucrose, glucose and fructose were extracted by pressing the stalks at dough stage (R4). The initial extracted syrup fermented faster than the control culture grown on a yeast extract/phosphate/sucrose medium. The syrup was subsequently concentrated 1.25–2.25 times, supplemented with urea, and fermented using Saccharomyces cerevisiae for up to 96 h. The final ethanol concentrations obtained were 8.1 % (v/v) to 15.6 % (v/v), equivalent to 90.3–92.2 % of the theoretical yields. However, fermentation productivity decreased with sugar concentration, suggesting that the yeast might be osmotically stressed at the increased sugar concentrations. These results provide in-depth information for utilizing tropical maize syrup for bioethanol production that will help in tropical maize breeding and development for use as another feedstock for the biofuel industry. 相似文献
80.
Joshua?C?KwekelEmail author Varsha?G?Desai Carrie?L?Moland Vikrant?Vijay James?C?FuscoeEmail author 《Biology of sex differences》2013,4(1):14