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91.
Tandon VK Kumar M Awasthi AK Saxena HO Goswamy GK 《Bioorganic & medicinal chemistry letters》2004,14(12):3177-3180
The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a dose of 5mg/kg iv in anaesthetized cats. 相似文献
92.
The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both individually and in combination, in reducing lead concentration in blood and soft tissues and in restoring lead induced altered biochemical variables in rats. Exposure to subacute dose of lead implicated a critical role of reactive oxygen species (ROS) and oxidative stress in altering the normal values of these variables. Exposure to lead caused a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis pathway and glutathione (GSH) level. These changes were also accompanied by inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS) activities in liver and changes in platelet counts in whole blood suggesting disturbed haem synthesis pathway. Lead exposure also led to a pronounced depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S-transferase (GST). Specific activities of membrane-bound enzymes, acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly inhibited on lead exposure. These biochemical changes were correlated with increased uptake of lead in blood and soft tissues. Post lead exposure treatment with MiADMSA in particular provided significant recovery in altered biochemical variables besides significant depletion of tissue lead burden. Treatment with CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue oxidative stress, although they were equally effective in the removal of tissue lead burden. Tissue zinc and copper levels did not depict any significant depletion, although changes like marked depletion of zinc following CaNa(2)EDTA and copper after MiADMSA administration were of some concern. Combined administration of CaNa(2)EDTA, particularly with MiADMSA, was the most effective treatment protocol compared to all other treatments. It can be concluded from our present results that combined therapy with CaNa(2)EDTA and MiADMSA proved significantly better in restoring biochemical and clinical variables over monotherapy with these chelating agents against subacute lead exposure in adult rats. 相似文献
93.
The effect of NaCl on two vital processes of cyanobacterial metabolism, viz. N(2) fixation and oxygenic photosynthesis, was studied in the cyanobacterium Nostoc muscorum grown diazotrophically. An increase in NaCl concentration suppressed the formation of heterocyst and adversely affected the nitrogenase activity in the parent, whereas in Li(+)-R and Na(+)-R mutants NaCl stress did not cause any adverse effect. The rate of photosynthetic O(2)-evolution was also adversely affected by the NaCl stress, but the magnitude was less than that of nitrogenase activity. L-Proline, the well-known osmoprotectant, provided protection to the cyanobacterium against NaCl stress. The parent strain utilized L-proline as a nitrogen source and suppressed heterocyst formation and nitrogenase activity, while mutants showed normal heterocyst frequency and nitrogenase activity. Therefore, it may be that the proline metabolism is altered as a result of mutation. The intracellular levels of proline in the parent were enhanced about threefold in the medium containing 1 mol x m(-3) proline, while in mutants there was no significant increase in the intracellular level of proline. In the medium containing both NaCl and proline, the intracellular level of proline was enhanced in the parent as well as in both mutant strains. This suggests that the parent strain possessed both normal proline uptake and salt-induced proline uptake systems, whereas the mutant strains were defective in normal proline uptake and had only salt-induced proline uptake. The over-accumulation of proline in the presence of NaCl stress is due either to the loss of proline oxidase activity or to the accumulation of exogenous proline. 相似文献
94.
Ni L Zheng XS Somers PK Hoong LK Hill RR Marino EM Suen KL Saxena U Meng CQ 《Bioorganic & medicinal chemistry letters》2003,13(4):745-748
alpha,beta-Unsaturated sulfones have been discovered from a combinatorial library as leads for a new series of inhibitors of inducible VCAM-1 expression. Although not essential, further conjugation of the sulfonyl group to another vinyl group or a phenyl group increases the potency dramatically. 相似文献
95.
Saxena AK Ram S Saxena M Singh N Prathipati P Jain PC Singh HK Anand N 《Bioorganic & medicinal chemistry》2003,11(9):2085-2090
A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series. 相似文献
96.
Singh I Prasad AK Sharma AK Saxena RK Olsen CE Cholli AL Samuelson LA Kumar J Watterson AC Parmar VS 《Bioorganic & medicinal chemistry》2003,11(4):529-538
Eleven (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins have been synthesised in two steps starting from the coupling of cinnamic acid/substituted cinnamic acid with appropriate phenols, followed by acetylation in 50-83% overall yields. All hydroxy- and acetoxycoumarins were unambiguously identified on the basis of their spectral data. Candida antarctica lipase-catalysed deacetylation of these racemic acetoxydihydrocoumarins in dioxane occurred with moderate enantioselectivity. This is one of the rare examples of resolution using phenolic ester moiety as a remote handle for chiral recognition by a lipase. 相似文献
97.
Using data on 9762 women from the 1997 Yemen Demographic and Maternal and Child Health Survey, this paper examines the prevalence and socioeconomic correlates of consanguineous marriages in Yemen. The results indicate that 40% of marriages are consanguineous, over 85% of which are between first cousins. The prevalence of consanguineous marriages appears to have increased over time, particularly for the last marriage cohort. As for socioeconomic correlates, the study confirms the inverse association between consanguineous marriages and women's education and occupation, age at marriage and economic status. However, no statistically significant difference in the prevalence of consanguinity has been found by place of residence and geographical region. Somewhat unexpected results have been obtained by husband's background characteristics, with higher educated men and those working in the modern sector of the economy being more likely to be married to cousins. 相似文献
98.
Effect of three chlorinated pesticides on hsromega stress gene in transgenic Drosophila melanogaster
Expression of hsromega stress gene in the third-instar larvae of 951-lacZ2 (hsromega-lacZ having-844pb sequence) and 498-lacZ1 (hrsomega-lacZ having -498bp sequence) strains of Drosophila melanogaster at LC(50) and lower dietary concentrations of hexachlorocyclohexane (HCH) pentachlorophenol (PCP), and endosulfan was examined in relation to larval mortality by beta galactosidase activity, vital dye staining, and salivary gland polytene chromosome puffing. Our results showed that both HCH and PCP at lower concentrations evoked strong hsromega stress gene expression in the larval tissues while endosulfan did not. On the other hand, puffing data revealed that endosulfan at lower doses, induced well-developed puff at the resident site (93D) of the hsromega gene but the transgenic sites (30B in 951-lacZ2 and 44B in 498-lacZ1 strain) did not show any well-developed puff. Regression in hsromega stress gene expression in 951-lacZ2 strain at LC(50) concentrations of HCH and PCP after 48 h was concurrent with extensive tissue damage as evident by trypan blue staining. Similarly, strong hsromega expression was accompanied by insignificant trypan blue staining in the larval tissues of this strain after shorter duration of exposure (2-12 h) to these toxicants. Although endosulfan under similar experimental condition did not induce hsromega, strong trypan blue staining indicated extensive tissue damage after 48 h of exposure. The present study suggests that all the three toxicants pose cytotoxic potential to Drosophila. While protective role of this stress gene was evident at the initial stages of exposure, extensive tissue damage in the later stages of intoxication accompanied by autorepression of hsromega led to larval mortality. The study further suggests that -844bp upstream sequence of the gene is adequate for hsromega inducibility against HCH and PCP but not for endosulfan for which responsive elements may be searched further upstream. 相似文献
99.
The mechanism of copper resistance in a multiple-metal-resistant natural isolate Pseudomonas putida strain S4 is based on inducible efflux. Active extrusion of copper ions occurs from the cytoplasm during the exponential phase of growth. Involvement of ATPase in the efflux of copper ions has been demonstrated by employing specific inhibitors. The effluxed copper is not thrown out of the cell, but remains in a bound form (to a protein) in the periplasm. Thus, a balance between the intracellular level, to fulfill the metabolic requirements, and the periplasmic sequestration, to evade toxicity, is maintained by this isolate. 相似文献
100.
Mukhopadhyay I Nazir A Mahmood K Saxena DK Das M Khanna SK Chowdhuri DK 《Cell biology and toxicology》2002,18(1):1-11
The effect of argemone oil on hsp70expression and tissue damage was investigated by studying β-galactosidase activity, Western blotting and hybridization, and
trypan blue staining in the larval tissues of transgenic Drosophila melanogaster(hsp70-lacZ)Bg
9. Different concentrations of argemone oil were mixed with food and third-instar larvae were allowed to feed on them for different
time intervals (2, 4, 24, and 48 h). Argemone oil was found to induce hsp70even in the lowest concentration of the adulterant while maximum tissue damage was observed in the higher two treatment groups.
Malpighian tubules and midgut tissue reflected maximum damage as evidenced by both high β-galactosidase activity and trypan
blue staining in these tissues. A prior temperature shock treatment to the larvae was enough to protect the larvae from argemone
oil-induced tissue damage as evidenced by little or no trypan blue staining. The present study suggests the cytotoxic potential
of argemone oil and further strengthens the evidence for the use of hsp70as a biomarker in risk assessment.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献