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81.
Mehul M. Patel Mimansha D. Mali Saurabh K. Patel 《Bioorganic & medicinal chemistry letters》2010,20(21):6324-6326
The condensation reaction of diphenylamine with 2-oxo-2H-(substituted chromen)-4-yl acetic acid in presence of anhydrous zinc chloride afford 4-(acridine-9-ylmethyl)-2H-(substituted chromen)-2-one. The synthesized compounds were characterized by spectral studies and elemental analysis and screened for their in vitro antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes (gram +ve), Escherichia coli, Pseudomonas aeruginosa (gram ?ve) and antifungal activity against Aspergillus niger and anticancer activity (HL-60, Hep-2 & HEK293T) by MTT assay. Chloro substituted compounds showed antimicrobial and anticancer activity with IC50 values in the low micromolar range. 相似文献
82.
Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and M2-M3 linker
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Acetylcholine receptor channel gating is a propagated conformational cascade that links changes in structure and function at the transmitter binding sites in the extracellular domain (ECD) with those at a "gate" in the transmembrane domain (TMD). We used Phi-value analysis to probe the relative timing of the gating motions of alpha-subunit residues located near the ECD-TMD interface. Mutation of four of the seven amino acids in the M2-M3 linker (which connects the pore-lining M2 helix with the M3 helix), including three of the four residues in the core of the linker, changed the diliganded gating equilibrium constant (K(eq)) by up to 10,000-fold (P272 > I274 > A270 > G275). The average Phi-value for the whole linker was approximately 0.64. One interpretation of this result is that the gating motions of the M2-M3 linker are approximately synchronous with those of much of M2 (approximately 0.64), but occur after those of the transmitter binding site region (approximately 0.93) and loops 2 and 7 (approximately 0.77). We also examined mutants of six cys-loop residues (V132, T133, H134, F135, P136, and F137). Mutation of V132, H134, and F135 changed K(eq) by 2800-, 10-, and 18-fold, respectively, and with an average Phi-value of 0.74, similar to those of other cys-loop residues. Even though V132 and I274 are close, the energetic coupling between I and V mutants of these positions was small (< or =0.51 kcal mol(-1)). The M2-M3 linker appears to be the key moving part that couples gating motions at the base of the ECD with those in TMD. These interactions are distributed along an approximately 16-A border and involve about a dozen residues. 相似文献
83.
Williams KD Blangero J Cottom CR Lawrence S Choh AC Czerwinski SA Lee M Duren DL Sherwood RJ Dyer TD Jha B Subedi J Williams-Blangero S Towne B 《Human biology; an international record of research》2007,79(6):609-622
Brachymesophalangia-V (BMP-V), a short and broad middle phalanx of the fifth digit, is the most common of all skeletal anomalies of the hand. When this feature appears alone, it is clinically known as brachydactyly type A3 (BDA3). A high prevalence of BDA3 has been observed among the children of the Jirel ethnic group in eastern Nepal. As part of the Jiri Growth Study, a hand-wrist radiograph is taken annually of each child to assess skeletal development. For this study the most recent radiographs of 1,357 Jirel children, adolescents, and young adults (676 boys, 681 girls), age 3-20 years, were examined for the presence or absence of BDA3, to report the prevalence and estimate the heritability of BDA3 in the Jirel population. The overall prevalence of BDA3 in this sample was 10.5% (12.9% of the males and 8.9% of the females were classified as BDA3 affected). The additive genetic heritability of BDA3 was statistically significant in this sample (h2 +/- SE = 0.87 +/- 0.16, p < 0.0001). This study is the first to estimate the prevalence and heritability of BDA3 in a large South Asian family-based sample. 相似文献
84.
Youssef D Nichols CE Cameron TS Balzarini J De Clercq E Jha A 《Bioorganic & medicinal chemistry letters》2007,17(20):5624-5629
A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have significant anticancer activity against representative murine and human cancer cell lines during in vitro bioassays. This corroborated with in vitro cytostatic activity against a panel of 60 cell lines studied at the National Cancer Institute (USA). 相似文献
85.
Fitzgerald JE Jha AK Colubri A Sosnick TR Freed KF 《Protein science : a publication of the Protein Society》2007,16(10):2123-2139
We developed a series of statistical potentials to recognize the native protein from decoys, particularly when using only a reduced representation in which each side chain is treated as a single C(beta) atom. Beginning with a highly successful all-atom statistical potential, the Discrete Optimized Protein Energy function (DOPE), we considered the implications of including additional information in the all-atom statistical potential and subsequently reducing to the C(beta) representation. One of the potentials includes interaction energies conditional on backbone geometries. A second potential separates sequence local from sequence nonlocal interactions and introduces a novel reference state for the sequence local interactions. The resultant potentials perform better than the original DOPE statistical potential in decoy identification. Moreover, even upon passing to a reduced C(beta) representation, these statistical potentials outscore the original (all-atom) DOPE potential in identifying native states for sets of decoys. Interestingly, the backbone-dependent statistical potential is shown to retain nearly all of the information content of the all-atom representation in the C(beta) representation. In addition, these new statistical potentials are combined with existing potentials to model hydrogen bonding, torsion energies, and solvation energies to produce even better performing potentials. The ability of the C(beta) statistical potentials to accurately represent protein interactions bodes well for computational efficiency in protein folding calculations using reduced backbone representations, while the extensions to DOPE illustrate general principles for improving knowledge-based potentials. 相似文献
86.
Jha A Mukherjee C Prasad AK Parmar VS Clercq ED Balzarini J Stables JP Manavathu EK Shrivastav A Sharma RK Nienaber KH Zello GA Dimmock JR 《Bioorganic & medicinal chemistry》2007,15(17):5854-5865
A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice. 相似文献
87.
Brassinin is a plant defense metabolite with antimicrobial activity produced de novo by a variety of Brassica species in response to stress, that is, a phytoalexin. The inhibition of brassinin oxidase (BO), a brassinin-detoxifying enzyme produced by the phytopathogenic fungus Leptosphaeria maculans, is a target in our continuing search for novel crop protection agents. To probe the substrate specificity of BO, in particular the mechanism of the detoxification step, several analogues of brassinin, including functional group isosteres ((mono/dithio)carbamate, urea, and thiourea) and homologue methyl tryptaminedithiocarbamate, were investigated using fungal cultures and purified BO. It was concluded that the essential structural features of substrates of BO were: (i) an -NH at the (mono/dithio)carbamate, urea or thiourea group; (ii) a methylene bridge between indole and the functional group; (iii) a methyl or ethyl group attached to the thiol moiety of the (mono/di)thiocarbamate group. A general stepwise pathway for the oxidation of brassinin was proposed that accounts for the structural requirements of detoxification of brassinin analogues in L. maculans. All compounds that were BO substrates appeared to be oxidized in mycelial cultures to aldehydes, except for the two most polar compounds N'-(3-indolylmethyl)-N'-methylurea and methyl N'-(3-indolylmethyl)carbamate. The substrate specificity of BO suggests that selective inhibitors can be designed for the potential control of L. maculans. 相似文献
88.
Ahlawat S Battan B Dhiman SS Sharma J Mandhan RP 《Journal of industrial microbiology & biotechnology》2007,34(12):763-770
A very high level of alkalophilic and thermostable pectinase and xylanase has been produced from newly isolated strains of
Bacillus subtilis and Bacillus pumilus respectively. Enzyme production for pectinase was carried out under SSF using combinations of cheap agricultural residues
while xylanase was produced under submerged fermentation using wheat bran as substrate to minimize the cost of production
of these enzymes Among the various substrates tested, the highest yield of pectinase production was observed by using combination
of WB + CW (6592 U/g of dry substrate) supplemented with 4% yeast extract when incubated at 37 °C for 72 h using deionized
water of pH 7.0 as moistening agent. The biobleaching effect of these cellulase free enzymes on kraft pulp was determined.
Both xylanase and pectinase showed stability over a broad range of pH from 6 to 10 and temperature from 55 to 70 °C. The bleaching
efficiency of the pectinase and xylanase on kraft pulp was maximum after 150 min at 60 °C using enzyme dosage of 5 IU/ml of
each enzyme at 10% pulp consistency with about 16% reduction in kappa number and 84% reduction in permanganate number. Enzyme
treated pulp when subjected to CDED1D2 steps, 25% reduction in chlorine consumption and upto 19% reduction in consumption of chlorine dioxide was observed for obtaining
the same %ISO brightness. Also an increase of 22 and 84% in whiteness and fluorescence respectively and a decrease of approximately
19% in the yellowness of the biotreated pulp were observed by pretreatment of the pulp with our enzymatic mixture. 相似文献
89.
Ethylene influences green plant regeneration from barley callus 总被引:3,自引:0,他引:3
The plant hormone ethylene is involved in numerous plant processes including in vitro growth and regeneration. Manipulating
ethylene in vitro may be useful for increasing plant regeneration from cultured cells. As part of ongoing efforts to improve
plant regeneration from barley (Hordeum vulgare L.), we investigated ethylene emanation using our improved system and investigated methods of manipulating ethylene to increase
regeneration. In vitro assays of regeneration from six cultivars, involving 10 weeks of callus initiation and proliferation
followed by 8 weeks of plant regeneration, showed a correlation between regeneration and ethylene production: ethylene production
was highest from ‘Golden Promise’, the best regenerator, and lowest from ‘Morex’ and ‘DH-20’, the poorest regenerators. Increasing
ethylene production by addition of 1-aminocyclopropane 1-carboxylic acid (ACC) during weeks 8–10 increased regeneration from
Morex. In contrast, adding ACC to Golden Promise cultures during any of the tissue culture steps reduced regeneration, suggesting
that Golden Promise may produce more ethylene than needed for maximum regeneration rates. Blocking ethylene action with silver
nitrate during weeks 5–10 almost doubled the regeneration from Morex and increased the Golden Promise regeneration 1.5-fold.
Silver nitrate treatment of Golden Promise cultures during weeks 8–14 more than doubled the green plant regeneration. These
results indicate that differential ethylene production is related to regeneration in the improved barley tissue culture system.
Specific manipulations of ethylene were identified that can be used to increase the green plant regeneration from barley cultivars.
The timing of ethylene action appears to be critical for maximum regeneration. 相似文献
90.