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11.
Singhal P Gaur A Behl V Gautam A Varshney B Paliwal J Batra V 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,852(1-2):293-299
A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of chloroquine, an antimalarial drug, in plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method is based on simple protein precipitation with methanol followed by a rapid isocratic elution with 10 mM ammonium acetate buffer/methanol (25/75, v/v, pH 4.6) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 320.3-->247.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 2.0-489.1 ng/mL for chloroquine in dog plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.4 and 2.0 ng/mL, respectively in 0.05 mL plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range of 2.0-489.1 ng/mL. A run time of 2.0 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully used to analyze samples of dog plasma during non-clinical study of chloroquine. 相似文献
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Integral membrane proteins constitute a major constituent of lipid bilayer both in prokaryotes and eukaryotes. The statistical
analysis was carried out to determine the bias in amino acid distribution between prokaryotic and eukaryotic integral membrane
proteins (pIntMPs and eIntMPs). Our results indicate that both pIntMPs and eIntMPs demonstrate the striking similarity in
amino acid distribution in their transmembrane and extramembranous region. pIntMPs have relatively greater functional importance
for Gly and Asn in comparison to eIntMPs. 相似文献
14.
Bainbridge J Madden L Essex D Binks M Malhotra R Paleolog EM 《Arthritis research & therapy》2007,9(6):R127
The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation,
and as such provides a valuable target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic inflammatory
disease associated with increased synovial vascularity, and hence is a potential therapeutic target for angiogenesis inhibitors.
We examined the use of PPI-2458, a selective non-reversible inhibitor of MetAP-2, in disease models of RA, namely acute and
chronic collagen-induced arthritis (CIA) in mice. Whilst acute CIA is a monophasic disease, CIA induced with murine collagen
type II manifests as a chronic relapsing arthritis and mimics more closely the disease course of RA. Our study showed PPI-2458
was able to reduce clinical signs of arthritis in both acute and chronic CIA models. This reduction in arthritis was paralleled
by decreased joint inflammation and destruction. Detailed mechanism of action studies demonstrated that PPI-2458 inhibited
human endothelial cell proliferation and angiogenesis in vitro, without affecting production of inflammatory cytokines. Furthermore, we also investigated release of inflammatory cytokines
and chemokines from human RA synovial cell cultures, and observed no effect of PPI-2458 on spontaneous expression of cytokines
and chemokines, or indeed on the angiogenic molecule vascular endothelial growth factor (VEGF). These results highlight MetAP-2
as a good candidate for therapeutic intervention in RA. 相似文献
15.
Vaish Swati Parveen Reshma Rajneesh Singh Nootan Gupta Divya Basantani Mahesh Kumar 《Journal of plant research》2022,135(6):823-852
Journal of Plant Research - Plant glutathione S-transferases are an ancient protein superfamily having antioxidant activity. These proteins are primarily involved in diverse plant functions such as... 相似文献
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Shue HJ Chen X Shih NY Blythin DJ Paliwal S Lin L Gu D Schwerdt JH Shah S Reichard GA Piwinski JJ Duffy RA Lachowicz JE Coffin VL Liu F Nomeir AA Morgan CA Varty GB 《Bioorganic & medicinal chemistry letters》2005,15(17):3896-3899
A series of novel five- and six-membered ring urea derivatives have been described as potent and selective NK1 receptor antagonists. Several compounds in this series exhibited good oral activity and brain penetration. Syntheses of these compounds are also described herein. 相似文献
18.
Kapoor V Paliwal D Baskar Singh S Mohanti BK Das SN 《Biochemical and biophysical research communications》2012,422(4):764-769
Autophagy is a physiologically regulated and evolutionary conserved process that plays a critical role in degradation of cytoplasmic proteins and other macromolecules within the lysosomes. Beclin-1, the mammalian orthologue of yeast Atg6, is an important mediator of autophagy that has been studied in many human cancers. However, the expression of Beclin-1 has not yet been investigated in oral cancer. We for the first time investigated the expression of Beclin-1 in serum and tissues and correlated it with the clinic-pathological features of oral cancer patients. m-RNA expression of Beclin-1 was evaluated in tumor and normal areas of surgical specimens from 10 oral cancer patients by real-time PCR. Approximately, 8-fold lower expression (p<0.001) of Beclin-1 mRNA was observed in tumor tissue as compared to the normal tissue. Serum levels of Beclin-1 were evaluated by SPR and ELISA. No significant difference was observed in serum Beclin-1 levels in patients as compared to healthy subjects, similarly no correlation was found between serum levels and clinic-pathological parameters such as stage, lymph node involvement and tumor size. Our results demonstrate that down-regulation of Beclin-1 may play an important role in the development and progression of oral cancer possibly by dysregulation of autophagy in tumor cells. 相似文献
19.
RR Pandey A Srivastava R Malasoni A Naqvi A Jain JP Maikhuri S Paliwal G Gupta AK Dwivedi 《Bioorganic & medicinal chemistry letters》2012,22(17):5735-5738
A series of twenty two derivatives of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one and their 2-methylene derivatives were synthesized from naturally abundant cinchonine (I). Tartarate salts of these compounds were prepared and evaluated for spermicidal activity. The most active compounds (24, 27, 34, 36, and 38) showing potent spermicidal activity were further evaluated against different strains of Trichomonas vaginalis, for antimicrobial activity, in HeLa cell lines for cytotoxicity and against Lactobacillus jensenii for eco-safety. The tartarate of 3-(1-pentyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one (27) was found to be more active than N-9 in spermicidal activity. 相似文献
20.
Inflammatory cytokine TNFα enhances permeability of brain capillaries constituting blood brain barrier (BBB). In the monoculture endothelial models of BBB TNFα alters tight junction (TJ) structure and protein content. Claudin-5 (Cldn5) is a key TJ protein whose expression in the brain endothelial cells is critical to the function of BBB. TNFα reduces Cldn5 promoter activity and mRNA expression in mouse brain derived endothelial cells but the regulatory elements and signaling mechanism involved are not defined. Here we report that TNFα acts through NFκB signaling and requires a conserved promoter region for the down-regulation of Cldn5 expression. Overexpression of the NFκB subunit p65 (RelA) alone repressed Cldn5 promoter activity in mouse brain endothelial cells. We observed partial loss of Cldn5 protein expression after prolonged TNFα treatment in primary endothelial culture isolated from C56BL/6 mice brain. Taken together, our results confirm and extend previous observations of TNFα induced down-regulation of Cldn5 expression in mouse brain endothelial cells. 相似文献