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81.
82.
Synthesis,Characterization, and Biological Activities of Pendant Arm‐Pyridyltetrazole Copper(II) Complexes: DNA Binding/Cleavage Activity and Cytotoxic Studies
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Shaik Mustafa Bommuluri Umamaheswara Rao Manubolu Surya Surendrababu Kalidindi Krishnam Raju Gollapalli Nageswara Rao 《化学与生物多样性》2015,12(10):1516-1534
2‐(1H‐Tetrazol‐5‐yl)pyridine ( L ) has been reacted separately with Me2NCH2CH2Cl?HCl and ClCH2CH2OH to yield two regioisomers in each case, N,N‐dimethyl‐2‐[5‐(pyridin‐2‐yl)‐1H‐tetrazol‐1‐yl]ethanamine ( L1 )/N,N‐dimethyl‐2‐[5‐(pyridin‐2‐yl)‐2H‐tetrazol‐2‐yl]ethanamine ( L2 ) and 2‐[5‐(pyridin‐2‐yl)‐1H‐tetrazol‐1‐yl]ethanol ( L3 )/2‐[5‐(pyridin‐2‐yl)‐2H‐tetrazol‐2‐yl]ethanol ( L4 ), respectively. These ligands, L1 – L4 , have been coordinated with CuCl2?H2O in 1 : 1 composition to furnish the corresponding complexes 1 – 4 . EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X‐ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on double‐stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free‐radical mechanism (OH ? ). In vitro anticancer activities of the complexes against MCF‐7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC50 values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin. 相似文献
83.
Divakara S. S. M. Uppu Goutham B. Manjunath Venkateswarlu Yarlagadda Jyothi E. Kaviyil Raju Ravikumar Krishnamoorthy Paramanandham Bibek R. Shome Jayanta Haldar 《PloS one》2015,10(3)
Gram-negative ‘superbugs’ such as New Delhi metallo-beta-lactamase-1 (bla
NDM-1) producing pathogens have become world’s major public health threats. Development of molecular strategies that can rehabilitate the ‘old antibiotics’ and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs) that restore the antibacterial efficacy (enhancement by >80-1250 fold) of tetracycline antibiotics towards bla
NDM-1
Klebsiella pneumonia and bla
NDM-1
Escherichia coli clinical isolates. Organismic studies showed that bacteria had an increased and faster uptake of tetracycline in the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover, bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards bla
NDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs. 相似文献
84.
85.
Joseph C. Y. Liu Janice M. Leung David A. Ngan Negar F. Nashta Silvia Guillemi Marianne Harris Viviane D. Lima Soo-Jung Um Yuexin Li Sheena Tam Tawimas Shaipanich Rekha Raju Cameron Hague Jonathon A. Leipsic Jean Bourbeau Wan C. Tan P. Richard Harrigan Don D. Sin Julio Montaner S. F. Paul Man 《PloS one》2015,10(4)
Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects. 相似文献
86.
Raju V. S. Rajala 《Molecular neurobiology》2010,42(1):39-47
The retina is an integral part of the central nervous system and retinal cells are known to express insulin receptors (IR),
although their function is not known. This article describes recent studies that link the photoactivation of rhodopsin to
tyrosine phosphorylation of the IR and subsequent activation of phosphoinositide 3-kinase, a neuron survival factor. Our studies
suggest that the physiological role of this process is to provide neuroprotection of the retina against light damage by activating
proteins that protect against stress-induced apoptosis. We focus mainly on our recently identified regulation of the IR pathway
through the G-protein-coupled receptor rhodopsin. Various mutant and knockout proteins of phototransduction cascade have been
used to study the light-induced activation of the retinal IR. Our studies suggest that rhodopsin may have additional previously
uncharacterized signaling functions in photoreceptors. 相似文献
87.
Icksoo Lee Alena Pecinova Petr Pecina Benjamin G. Neel Toshiyuki Araki Raju Kucherlapati Amy E. Roberts Maik Hüttemann 《生物化学与生物物理学报:疾病的分子基础》2010,1802(2):275-283
Noonan syndrome (NS) is an autosomal dominant disorder, and a main feature is congenital heart malformation. About 50% of cases are caused by gain-of-function mutations in the tyrosine phosphatase SHP2/PTPN11, a downstream regulator of ERK/MAPK. Recently it was reported that SHP2 also localizes to the mitochondrial intercristae/intermembrane space (IMS), but the role of SHP2 in mitochondria is unclear. The mitochondrial oxidative phosphorylation (OxPhos) system provides the vast majority of cellular energy and produces reactive oxygen species (ROS). Changes in ROS may interfere with organ development such as that observed in NS patients. Several phosphorylation sites have been found in OxPhos components including cytochrome c oxidase (CcO) and cytochrome c (Cytc), and we hypothesized that OxPhos complexes may be direct or indirect targets of SHP2. We analyzed mitochondrial function using mouse fibroblasts from wild-types, SHP2 knockdowns, and D61G SHP2 mutants leading to constitutively active SHP2, as found in NS patients. Levels of OxPhos complexes were similar except for CcO and Cytc, which were 37% and 28% reduced in the D61G cells. However, CcO activity was significantly increased, as we also found for two lymphoblast cell lines from NS patients with two independent mutations in PTPN11. D61G cells showed lower mitochondrial membrane potential and 30% lower ATP content compared to controls. ROS were significantly increased; aconitase activity, a marker for ROS-induced damage, was decreased; and catalase activity was increased in D61G cells. We propose that decreased energy levels and/or increased ROS may explain, at least in part, some of the clinical features in NS that overlap with children with mitochondrial disorders. 相似文献
88.
This study concerns 39 different grass species occurring in the wetland regions of Godavari delta in the west Godavari district (16°15′–17°30′N and 80°50′–81°55′E) of Andhra Pradesh, southern India. In each species, the sexual status of lemmas, the period of stigma receptivity, pollen/ovule ratio, pollen longevity and daily pollen release were examined. The functional sexual systems were determined after performing controlled pollinations and testing seed quality by weight and germination potential. The florets of 35 species are morphologically hermaphroditic. Among the other four species, Chionachne koenigii and Iseilema laxum are monoecious; Chrysopogon aciculatus and Pennisetum pedicellatum are andromonoecious. Examination of the sequential opening of florets and controlled pollinations revealed that C. koenigii and I. laxum are obligate outcrossers with incompatibility to geitonogamous pollen; C. aciculatus and P.pedicellatum have a high level of compatibility to xenopollen. These and another nine species were treated as predominantly outcrossing species. Yet another five species were predominantly self‐fertilized, while the remaining 21 species displayed a mixed breeding system. In a majority of the species the P/O ratios are not high and thus do not conform to the expected large P/O ratios in wind‐pollinated plants and postulated breeding systems except in a few species. The majority of these grasses shed pollen over a short period spreading from 2 am to 8 am, when usually low turbulent conditions exist, thus allowing short distance transport and restricted pollen shadows with higher concentration of pollen near the source. This appears to be the appropriate strategy for maximization of pollination in view of the short lifespan of pollen that extends mostly over 1–3 h period, and the patchy distribution of the grasses under study. The restricted pollen shadows facilitate the low levels of pollen production in the grass species under study to fertilize most or all the available ovules. 相似文献
89.
Selvam R Ganesan K Narayana Raju KV Gangadharan AC Manohar BM Puvanakrishnan R 《Life sciences》2007,80(26):2403-2410
Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 μg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca2+ ATPase (PMCA) activity was inhibited while intracellular Ca2+ level as well as prostaglandin E2 levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hz × 4 μT × 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca2+ levels in blood lymphocytes subsequently inhibiting PGE2 biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings. 相似文献
90.