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131.
Reddy DK Shekhar V Prabhakar P Babu DC Ramesh D Siddhardha B Murthy US Venkateswarlu Y 《Bioorganic & medicinal chemistry letters》2011,21(3):997-1000
A simple, first stereoselective total synthesis of botryolide-E has been described. The synthesis started from propylene oxide employing Jacobsen’s hydrolytic kinetic resolution (HKR), selective epoxide opening, sharpless asymmetric dihydroxylation, one pot acetonide deprotection and lactonization as key steps. Further, the synthesis confirms the absolute configuration of the natural product botryolide-E and we evaluated the biological behavior of natural product botryolide-E against a panel of bacteria and fungi. Botryolide-E exhibits significant potent activity against Staphylococcus aureus (MTCC 96) (6.25 μg/ml), good against Escherichia coli (MTCC 443) (12.5 μg/ml), Bacillus subtilis (MTCC 441) (25 μg/ml) and compound 1 exhibited good to moderate antifungal activity. 相似文献
132.
Saiko P Graser G Madlener S Schwarz S Krupitza G Jaeger W Somepalli V Golakoti T Fritzer-Szekeres M Szekeres T 《Nucleosides, nucleotides & nucleic acids》2011,30(12):1190-1196
Digalloylresveratrol (DIG) is a newly synthesized agent aimed to combine the biological effects of the natural compounds, gallic acid and resveratrol, which both are free radical scavengers exhibiting anticancer activity. In this study, we investigated the effects of DIG on the growth of human HL-60 leukemia cells and on the colony formation of human BxPC-3 and PANC-1 pancreatic cancer cells. DIG was applied alone and in combination with arabinofuranosylcytosine (Ara-C) or difluorodeoxycytidine (dFdC), depending on the cell line employed. All IC(50) values observed were in the low micromolar range rendering DIG a promising antitumor compound in vitro. Considering the combination experiments, DIG yielded additive effects with Ara-C in HL-60 cells and-to a lesser extent-with dFdC in BxPC-3 and PANC-1 cells. Owing to our results, DIG may be further investigated in vitro and in animals. 相似文献
133.
Subhadra Nandakumar Sunil Kannanganat Karen M. Dobos Megan Lucas John S. Spencer Sunan Fang Melissa A. McDonald Jan Pohl Kristin Birkness Venkateswarlu Chamcha Melissa V. Ramirez Bonnie B. Plikaytis James E. Posey Rama Rao Amara Suraj B. Sable 《PLoS pathogens》2013,9(10)
Glycosylation is the most abundant post-translational polypeptide chain modification in nature. Although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of B cell epitopes, the role in T cell immunity is not completely understood. Here, using ELISPOT and polychromatic flow cytometry, we show that O-mannosylation of the adhesin, Apa, of Mycobacterium tuberculosis (Mtb) is crucial for its T cell antigenicity in humans and mice after infection. However, subunit vaccination with both mannosylated and non-mannosylated Apa induced a comparable magnitude and quality of T cell response and imparted similar levels of protection against Mtb challenge in mice. Both forms equally improved waning BCG vaccine-induced protection in elderly mice after subunit boosting. Thus, O-mannosylation of Apa is required for antigenicity but appears to be dispensable for its immunogenicity and protective efficacy in mice. These results have implications for the development of subunit vaccines using post-translationally modified proteins such as glycoproteins against infectious diseases like tuberculosis. 相似文献
134.
135.
Yihui Tu Huaming Xue Wendy Francis Andrew P. Davies Ian Pallister Venkateswarlu Kanamarlapudi Zhidao Xia 《Biochemical and biophysical research communications》2013
Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti-inflammatory and analgesic effect. However, Dex also has many side effects following repeated use over prolonged periods mainly through increasing apoptosis and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic effect on many cells and little is known about its effect on OA chondrocytes. Therefore, the aim of this study is to investigate whether LF can inhibit Dex-induced OA chondrocytes apoptosis and explore its possible molecular mechanism involved in. MTT assay was used to determine the optimal concentration of Dex and recombinant human LF (rhLF) on chondrocytes at different time and dose points. Chondrocytes were then stimulated with Dex in the absence or presence of optimal concentration of rhLF. Cell proliferation and viability were evaluated using MTT and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi-parameter apoptosis assay kit using both confocal microscopy and flow cytometry, respectively. The expression of extracellular signal-regulated kinase (ERK), FAS, FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The optimal concentration of Dex (25 μg/ml) and rhLF (200 μg/ml) were chosen for the following experiments. rhLF significantly reversed the detrimental effect of Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF significantly prevented Dex-induced down-regulation of ERK and up-regulation of FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as an anabolic effect on chondrocytes through significantly reversing Dex-induced chondrocytes apoptosis. This study may contribute to further investigating the clinical application of LF on OA. 相似文献
136.
Venkateswarlu Popuri Jing Huang Mahesh Ramamoorthy Takashi Tadokoro Deborah L. Croteau Vilhelm A. Bohr 《Nucleic acids research》2013,41(2):881-899
Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases. 相似文献
137.
Background
Iron is an essential micronutrient for all organisms because it is a component of enzyme cofactors that catalyze redox reactions in fundamental metabolic processes. Even though iron is abundant on earth, it is often present in the insoluble ferric [Fe (III)] state, leaving many surface environments Fe-limited. The haploid green alga Chlamydomonas reinhardtii is used as a model organism for studying eukaryotic photosynthesis. This study explores structural and functional changes in PSI-LHCI supercomplexes under Fe deficiency as the eukaryotic photosynthetic apparatus adapts to Fe deficiency.Results
77K emission spectra and sucrose density gradient data show that PSI and LHCI subunits are affected under iron deficiency conditions. The visible circular dichroism (CD) spectra associated with strongly-coupled chlorophyll dimers increases in intensity. The change in CD signals of pigments originates from the modification of interactions between pigment molecules. Evidence from sucrose gradients and non-denaturing (green) gels indicates that PSI-LHCI levels were reduced after cells were grown for 72 h in Fe-deficient medium. Ultrafast fluorescence spectroscopy suggests that red-shifted pigments in the PSI-LHCI antenna were lost during Fe stress. Further, denaturing gel electrophoresis and immunoblot analysis reveals that levels of the PSI subunits PsaC and PsaD decreased, while PsaE was completely absent after Fe stress. The light harvesting complexes were also susceptible to iron deficiency, with Lhca1 and Lhca9 showing the most dramatic decreases. These changes in the number and composition of PSI-LHCI supercomplexes may be caused by reactive oxygen species, which increase under Fe deficiency conditions.Conclusions
Fe deficiency induces rapid reduction of the levels of photosynthetic pigments due to a decrease in chlorophyll synthesis. Chlorophyll is important not only as a light-harvesting pigment, but also has a structural role, particularly in the pigment-rich LHCI subunits. The reduced level of chlorophyll molecules inhibits the formation of large PSI-LHCI supercomplexes, further decreasing the photosynthetic efficiency. 相似文献138.
Shanker AK Djanaguiraman M Venkateswarlu B 《Metallomics : integrated biometal science》2009,1(5):375-383
Chromium has received relatively little attention from plant scientists compared to other heavy metals in recent times in spite of it being a very a hazardous environmental pollutant. One of the reasons for this is the complexity of the metal's interactions with biological systems and the difficulty in studying them. Although the possible mode of entry into the plants, resultant toxicity mechanisms and tolerance potential has been worked out in plants there is still a need to get a complete picture of the Cr-plant interactome. With the advent of hyphenated technologies and global gene/protein and metabolite expression/quantification techniques, studies to elucidate the complete metallome are possible albeit resource intensive. This minireview focuses on the recent developments in the field of Cr-plant interactions and proposes a model using a systems biology and integrated -omics approach to decipher the intricacies of Cr-plant interaction. 相似文献
139.
A gastro retentive floating drug delivery system with multiple-unit minitab’s based on gas formation technique was developed
in order to prolong the gastric residence time and to increase the overall bioavailability of the drug. The system consists
of the drug-containing core units prepared by direct compression process, which are coated with three successive layers of
an inner seal coat, effervescent layer (sodium bicarbonate) and an outer gas-entrapped polymeric membrane of an polymethacrylates
(Eudragit RL30D, RS30D, and combinations of them). Only the system using Eudragit RL30D and combination of them as a gas-entrapped
polymeric membrane could float. The time to float decreased as amount of the effervescent agent increased and coating level
of gas-entrapped polymeric membrane decreased. The optimum system floated completely within 3 min and maintained the buoyancy
over a period of 12 h. The drug release was controlled and linear with the square root of time. Increasing coating level of
gas-entrapped polymeric membrane decreased the drug release. Both the rapid floating and the controlled release properties
were achieved in the multiple-unit floating drug delivery system developed in this present study. The analysis of the parameter
dissolution data after storage at 40 °C and 75% RH for 3 months showed, no significant change indicating the two dissolution
profiles were considered to be similar (f2 value is more than 50). 相似文献
140.
Meka Lingam Thadisetty Ashok Vobalaboina Venkateswarlu Yamsani Madhusudan Rao 《AAPS PharmSciTech》2008,9(4):1253-1261
A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique
was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists
of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter
were coated with three successive layers, one of which is seal coat, an effervescent (sodium bicarbonate) layer, and an outer
polymeric layer of polymethacrylates. The formulations were evaluated for quality control tests, and all the parameters evaluated
were within the acceptable limits. The system using Eudragit RL30D and combination of them as polymeric layer could float
within acceptable time. The drug release was linear with the square root of time. The rapid floating and the controlled release
properties were achieved in this present study. When compared with the theoretical release profile, the similarity factor
of formulation with coating of RS:RL (1:3)–7.5%, was observed to be 74, which is well fitted into zero-order kinetics confirming
that the release from formulation is close to desired release profile. The stability samples showed no significant change
in dissolution profiles (p > 0.05). In vivo gastric residence time was examined by radiograms, and it was observed that the units remained in the stomach for about 5 h. 相似文献