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61.
In order to determine the structural requirements for cytotoxicity against various tumor cell lines, a new series of 16E-arylidene androstene amides with varying degrees of unsaturation in ring A has been synthesized. Characterization and invitro cytotoxic studies of the newly synthesized compounds are discussed. The compounds on evaluation against various tumor cell lines exhibited significant growth inhibition on leukemia cell lines. 3-Chloro-16E-{[4-(4-methylpiperazin-1-yl)-2-oxoethoxy]benzylidene}androst-5-en-17-one (10) emerged as the most potent compound of the series with GI(50) values of 3.94, 2.61, 6.90 and 1.79μM against CCRF-CEM, K-562, RPMI-8226 and SR leukemia cell lines, respectively. 相似文献
62.
Juan Pablo Gomez-Escribano Jean Franco Castro Valeria Razmilic Govind Chandra Barbara Andrews Juan A. Asenjo Mervyn J. Bibb 《BMC genomics》2015,16(1)
Background
Next Generation DNA Sequencing (NGS) and genome mining of actinomycetes and other microorganisms is currently one of the most promising strategies for the discovery of novel bioactive natural products, potentially revealing novel chemistry and enzymology involved in their biosynthesis. This approach also allows rapid insights into the biosynthetic potential of microorganisms isolated from unexploited habitats and ecosystems, which in many cases may prove difficult to culture and manipulate in the laboratory. Streptomyces leeuwenhoekii (formerly Streptomyces sp. strain C34) was isolated from the hyper-arid high-altitude Atacama Desert in Chile and shown to produce novel polyketide antibiotics.Results
Here we present the de novo sequencing of the S. leeuwenhoekii linear chromosome (8 Mb) and two extrachromosomal replicons, the circular pSLE1 (86 kb) and the linear pSLE2 (132 kb), all in single contigs, obtained by combining Pacific Biosciences SMRT (PacBio) and Illumina MiSeq technologies. We identified the biosynthetic gene clusters for chaxamycin, chaxalactin, hygromycin A and desferrioxamine E, metabolites all previously shown to be produced by this strain (J Nat Prod, 2011, 74:1965) and an additional 31 putative gene clusters for specialised metabolites. As well as gene clusters for polyketides and non-ribosomal peptides, we also identified three gene clusters encoding novel lasso-peptides.Conclusions
The S. leeuwenhoekii genome contains 35 gene clusters apparently encoding the biosynthesis of specialised metabolites, most of them completely novel and uncharacterised. This project has served to evaluate the current state of NGS for efficient and effective genome mining of high GC actinomycetes. The PacBio technology now permits the assembly of actinomycete replicons into single contigs with >99 % accuracy. The assembled Illumina sequence permitted not only the correction of omissions found in GC homopolymers in the PacBio assembly (exacerbated by the high GC content of actinomycete DNA) but it also allowed us to obtain the sequences of the termini of the chromosome and of a linear plasmid that were not assembled by PacBio. We propose an experimental pipeline that uses the Illumina assembled contigs, in addition to just the reads, to complement the current limitations of the PacBio sequencing technology and assembly software.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1652-8) contains supplementary material, which is available to authorized users. 相似文献63.
64.
ZnS:Mn nanoparticles were prepared by a chemical precipitation method and characterized by X‐ray diffraction (XRD), field emission gun scanning electron microscope (FEGSEM), and high resolution transmission electron microscopy (HRTEM). Capping agent (mercaptoethanol) concentrations used were 0 M, 0.005 M, 0.01 M, 0.015 M, 0.025 M, 0.040 M, and 0.060 M, and resulted in nanoparticles sizes of 2.98 nm, 2.9 nm, 2.8 nm, 2.7 nm, 2.61 nm, 2.2 nm and 2.1 nm, respectively. The thermoluminescence (TL) glow curve was recorded by heating the sample exposed to UV‐radiation, at a fixed heating rate 1°C sec–1. The TL intensity initially increased with temperature, attained a peak value Im for a particular temperature, and then decreased with further increase in temperature. The peak TL intensity increased with decreasing nanoparticle size, whereas the temperature corresponding to the peak TL intensity decreased slightly with reducing nanocrystal size. As a consequence of increase in surface‐to‐volume ratio and increased carrier recombination rates, the TL intensity increased with decreasing nanoparticle size. It was found that, whereas activation energy slightly decreased with decreasing nanoparticle size, the frequency factor decreased significantly with reduction in nanoparticle size. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
65.
Subash Chandra Gupta Hifzur Rahman Siddique Neeraj Mathur Achchhe Lal Vishwakarma Ranjit Kishore Mishra Daya Krishna Saxena Debapratim Kar Chowdhuri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
We examined a hypothesis that reactive oxygen species (ROS) generated by organophosphate compound dichlorvos modulates Hsp70 expression and anti-oxidant defense enzymes and acts as a signaling molecule for apoptosis in the exposed organism. Dichlorvos (0.015–15.0 ppb) without or with inhibitors of Hsp70, superoxide dismutase (SOD) and catalase (CAT) were fed to the third instar larvae of Drosophila melanogaster transgenic for hsp70 (hsp70-lacZ) Bg9 to examine Hsp70 expression, oxidative stress and apoptotic markers. A concentration- and time-dependent significant increase in ROS generation accompanied by a significant upregulation of Hsp70 preceded changes in antioxidant defense enzyme activities and contents of glutathione, malondialdehyde and protein carbonyl in the treated organisms. An inhibitory effect on SOD and CAT activities significantly upregulated ROS generation and Hsp70 expression in the exposed organism while inhibition of Hsp70 significantly affected oxidative stress markers induced by the test chemical. A comparison made among ROS generation, Hsp70 expression and apoptotic markers showed that ROS generation is positively correlated with Hsp70 expression and apoptotic cell death end points indicating involvement of ROS in the overall adversity caused by the test chemical to the organism. The study suggests that (a) Hsp70 and anti-oxidant enzymes work together for cellular defense against xenobiotic hazard in D. melanogaster and (b) free radicals may modulate Hsp70 expression and apoptosis in the exposed organism. 相似文献
66.
Das BB Sen N Roy A Dasgupta SB Ganguly A Mohanta BC Dinda B Majumder HK 《Nucleic acids research》2006,34(4):1121-1132
Emergence of the bi-subunit topoisomerase I in the kinetoplastid family (Trypanosoma and Leishmania) has brought a new twist in topoisomerase research related to evolution, functional conservation and preferential sensitivities to the specific inhibitors of type IB topoisomerase family. In the present study, we describe that naturally occurring flavones baicalein, luteolin and quercetin are potent inhibitors of the recombinant Leishmania donovani topoisomerase I. These compounds bind to the free enzyme and also intercalate into the DNA at a very high concentration (300 µM) without binding to the minor grove. Here, we show that inhibition of topoisomerase I by these flavones is due to stabilization of topoisomerase I–DNA cleavage complexes, which subsequently inhibit the religation step. Their ability to stabilize the covalent topoisomerase I–DNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT). However, in contrast to CPT, baicalein and luteolin failed to inhibit the religation step when the drugs were added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and CPT led us to investigate the effect of baicalein and luteolin on CPT-resistant mutant enzyme LdTOP1Δ39LS lacking 1–39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335–16344]. Baicalein and luteolin stabilize duplex oligonucleotide cleavage with LdTOP1Δ39LS. This observation was further supported by the stabilization of in vivo cleavable complex by baicalein and luteolin with highly CPT-resistant L.donovani strain. Taken together, our data suggest that the interacting amino acid residues of topoisomerase I may be partially overlapping or different for flavones and CPT. This study illuminates new properties of the flavones and provide additional insights into the ligand binding properties of L.donovani topoisomerase I. 相似文献
67.
Soh MA Garrett SH Somji S Dunlevy JR Zhou XD Sens MA Bathula CS Allen C Sens DA 《Cancer cell international》2011,11(1):41-12
Background
Neuron specific enolase (ENO2, γ-enolase) has been used as a biomarker to help identify neuroendocrine differentiation in breast cancer. The goal of the present study was to determine if ENO2 expression in the breast epithelial cell is influenced by the environmental pollutants, arsenite and cadmium. Acute and chronic exposure of MCF-10A cells to As+3 and Cd+2 sufficient to allow colony formation in soft agar, was used to determine if ENO2 expression was altered by these pollutants.Results
It was shown that both As+3 and Cd+2 exposure caused significant increases in ENO2 expression under conditions of both acute and chronic exposure. In contrast, ENO1, the major glycolytic enolase in non-muscle and neuronal cells, was largely unaffected by exposure to either As+3 or Cd+2. Localization studies showed that ENO2 in the MCF-10A cells transformed by As+3 or Cd+2 had both a cytoplasmic and nuclear localization. In contrast, ENO1 was localized to the cytoplasm. ENO2 localized to the cytoplasm was found to co-localized with ENO1.Conclusion
The results are the first to show that ENO2 expression in breast epithelial cells is induced by acute and chronic exposure to As+3 or Cd+2. The findings also suggest a possible link between As+3 and Cd+2 exposure and neuroendocrine differentiation in tumors. Overall, the results suggest that ENO2 might be developed as a biomarker indicating acute and/or chronic environmental exposure of the breast epithelial cell to As+3 and Cd+2. 相似文献68.
Vanadium toxicity is a challenging problem to the health professionals and a cutting-edge medical problem. Vanadium has been
recognized as industrial hazards that adversely affect human and animal reproductive health. Since testicular function is
exquisitely susceptible to reactive-oxygen species, the present study elucidates the possible involvement of oxidative stress
in vanadium-induced testicular toxicity and the prophylactic effects of vitamin E acetate against such adverse effects of
vanadium. The study also characterizes the effects of vanadium on rat adrenal steroidogenesis and determines the underlying
mechanisms of testicular and adrenal interactions in response to vanadium exposure. Significantly reduced sperm count associated
with decreased serum testosterone and gonadotropins level in the vanadium-injected group of rats compared to control substantially
proves the ongoing damaging effects of vanadium-induced ROS on developing germ cells. This is in turn reflected in the appreciable
increase in testicular lipid peroxidation level and decline in the activities of steroidogenic and antioxidant enzymes. However,
oral administration of vitamin E acetate could protect testes from the toxic effects of vanadium. Vanadium also results in
adrenocortical hyperactivity, as evidenced by the elevated secretion of glucocorticoids, adrenal gland hypertrophy and increased
activity of adrenal Δ53β-HSD. However, reversibility of these alterations in adrenocortical activities was vividly reflected after vitamin E acetate
supplementation. All these studies reveal that oxidative stress is the major mechanism of health deterioration and that vanadium
can act as a stressor metal causing chronic stress effects through excitation of hypothalamo-pituitary-adrenal axis. However
antioxidant support by vitamin E acetate may provide significant protection. 相似文献
69.
70.
Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans. 总被引:3,自引:0,他引:3
Nicolas Moniaux Grish Chandra Varshney Subhash Chand Chauhan Marie Christine Copin Maneesh Jain Uwe A Wittel Mahefatiana Andrianifahanana Jean-Pierre Aubert Surinder Kumar Batra 《The journal of histochemistry and cytochemistry》2004,52(2):253-261
We have previously cloned the full-length cDNA (approximately 28 Kb) and established the complete genomic organization (25 exons/introns over 100 kb) of the human MUC4 mucin. This large molecule is predicted to protrude over 2 microm above the cell surface, in which MUC4alpha is an extracellular mucin-type glycoprotein subunit and MUC4beta is the transmembrane subunit. Over two thirds of the encoded protein sequence consists of 16-amino-acid tandem repeats (TR), which are flanked by unique sequences. In this study we generated and characterized monoclonal antibodies (MAbs) directed against the TR region of MUC4. Mice were immunized with a KLH-conjugated MUC4 TR peptide, STGDTTPLPVTDTSSV. Several clones were purified by three rounds of limited dilutions and stable clones presenting a sustained antibody production were selected for subsequent characterization. Antibodies were tested for their reactivity and specificity to recognize the MUC4 peptide and further screened by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. One of the MAbs (8G7) was strongly reactive against the MUC4 peptide and with native MUC4 from human tissues or pancreatic cancer cells in Western blotting, immunohistochemistry, and confocal analysis. Anti-MUC4 MAb may represent a powerful tool for the study of MUC4 function under normal and pathological conditions and for diagnosis of solid tumors including those in the breast, pancreas, lungs, and ovaries. 相似文献