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941.
Inderjit S. Yadav Prajwal P. Nandekar Shambhavi Shrivastava Abhay Sangamwar Ashok Chaudhury Subhash Mohan Agarwal 《Gene》2014
Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is an attractive target for cancer therapy. Despite a number of effective EGFR inhibitors that are constantly expanding and different methods being employed to obtain novel compounds, the search for newer EGFR inhibitors is still a major scientific challenge. In the present study, a molecular docking and molecular dynamics investigation has been carried out with an ensemble of EGFR-TK structures against a synthetically feasible library of curcumin analogs to discover potent EGFR inhibitors. To resolve protein flexibility issue we have utilized 5 EGFR wild type crystal structures during docking as this gives improved possibility of identifying an active compound as compared to using a single crystal structure. We then identified five curcumin analogs representing different scaffolds that can serve as lead molecules. Finally, the 5 ns molecular dynamics simulation shows that knoevenagel condensate of curcumin specifically C29 and C30 can be used as starting blocks for developing effective leads capable of inhibiting EGFR. 相似文献
942.
943.
Metarhizium anisopliae was mass cultured on tapioca chips and rice bran, supplemented with waste fish meal extract or urea, in specially designed
large aluminium vessels. 相似文献
944.
A cobalt-resistant strain of Neurospora crassa (cor) was obtained by repeated subculturing of the wild type on cobalt-containing agar medium. N. crassa cor is twentyfold more resistant to cobalt ions compared with the wild type. Resistance was stable on repeated subculturing of cor on cobalt-free media. N. crassa cor is also cross-resistant to nickel (fourfold), but not to zinc or copper. Higher concentrations of iron and magnesium ions are required to reverse growth inhibition due to cobalt toxicity in N. crassa cor, compared with the wild type. Germinating conidia and mycelia of the cor strain accumulated lower levels of cobalt ions compared with the parent N. crassa. The partial transport block for cobalt uptake is shown to be primarily due to decreased surface binding of cobalt to mycelia and cell walls. Efflux of mycelial cobalt was also observed in wild type and cobalt-resistant N. crassa. The characteristics of cor in comparison with wild type N. crassa are discussed in relation to the mechanisms of cobalt resistance. 相似文献
945.
Cerebrospinal fluid (CSF) from twenty three patients with non specific mental retardation and fourteen age matched normal samples was subjected for qualitative analysis of protein profiles by two-dimensional gel electrophoresis (2-DE) and the proteins were visualised by ultra sensitive silver staining. Two proteins designated as mental retardation associated proteins (MRAP-I and MRAP-II) were identified in six male patients out of twenty three patients CSF samples. MRAP-I had an isoelectric point of 7.4 with a relative molecular weight 16.5 kDa, while MRAP-II had an iso-electric point of 7.2 with a relative molecular weight 16.8 kDa. The two proteins are presumed to be originated from brain, as they could not be traced in the serum of patients, nor due to proteolytic degradation. Despite unknown origin and identity, their presence in the CSF of a specific group of mentally retarded male patients suggest their possible clinical utility and to define protein alterations in mental retardation. 相似文献
946.
Richard Arthur Dixon Prakash Mohan Dey Ian Michael Whitehead 《Biochimica et Biophysica Acta (BBA)/General Subjects》1982,715(1):25-33
Chalcone isomerase (EC 5.5.1.6) from cell suspension cultures of Phaseolus vulgaris has been purified about 400-fold. The molecular weight, as estimated by gel-filtration and SDS-polyacrylamide gel electrophoresis, is approx. 28 000. No isoenzymic forms are observed. The enzyme, which appears to require no cofactors, catalyses the isomerisation of both 6′-hydroxy and 6′-deoxy chalcones to the corresponding flavones. Likewise, a range of both 5-hydroxy and 5-deoxy flavonoids and isoflavonoids act as competitive inhibitors. The most potent inhibitors include the naturally occurring antimicrobial comcpounds kievitone (Ki 9.2 μM) and coumestrol (Ki 2.5 μM). The kinetics of the isomerisation of 2′,4,4′-trihydroxychalcone to the flavanone liquiritigenin have been investigated at a range of pH values. The pH optimum was around 8.0 and Km changed with pH in a manner consistent with control by groups which ionise with pKa values of 7.05 and 8.7 respectively. At pH 8.0, the energy of activation was 17.56 kJ/mol in the range 25–40°C. The role of the enzyme in the induced accumulation of flavonoid/isoflavonoid derivatives inthe Frech bean in discussed. 相似文献
947.
Summary A novel nickel resistant, hyperaccumulatingN.crassa nir-2 mutant, isolated by us, sequestered 90% of Ni2+ from medium with 120 mg/l Ni2+. The parent wild strain showed comparable efficiency only at much lower concentrations (<10mg/l). The initial rapid rate and efficiency of Ni2+ removal could be maintained beyond 2 h by fresh addition of mycelial biomass. The results have been discussed from the stand point of the utility of metal resistant fungi in the control of environmental pollution. 相似文献
948.
The cell cycle remains an attractive target for the development of small-molecule inhibitors for use as both novel chemotherapeutics and research probes. Given the importance of cytoskeletal dynamics and cyclin-dependent kinases for cell-cycle progression, much interest has focused on the identification of anti-mitotic agents and kinase inhibitors. However recent advances in cell-based screening technologies and an increased interest in inhibitors with greater specificity are beginning to influence the search for novel cell-cycle inhibitors. 相似文献
949.
Xiaodong Wang Vishnu Priya Veeraraghavan Surapaneni Krishna Mohan Feng Lv 《Saudi Journal of Biological Sciences》2021,28(8):4522-4531
In worldwide, one of the most important cancer-related death is lung cancer. Also has the highest mortality rate between various cancer types. The count of lung cancer occurrence is increasing with an increased frequency by smoking. Proficient chemoprevention approaches are needed to prevent the occurrence of lung cancer. Therefore, the aim of this exploration is to determine the therapeutic impact on the immune modulatory effect of rhaponticin on lung tumorigenesis in vivo and in vitro cytotoxicity effect in A549 cells of human lung cancer. Lung cancer tumorigenesis in mice was challenged with benzo(a)pyrene (BaP) with 50 mg/kg bodyweight (b.wt) as oral administration for 6 weeks (two times/week). Rhaponticin were given orally 30 mg/kg b.wt (two times/week) in BaP induced mice from 12 weeks to 18 weeks. After treatment completes, the body weight was measured and then blood, lung tissue was collected for various parameters detection. The results evidenced that BaP induced mice decreased the bodyweight, increased lung weight, increased tumor markers (AHH, CEA and LDH), and increased the proinflammatory cytokines. The enzyme catalase, superoxide dismutase activity was decreased and increased lipid peroxidation in immune comprising cells compared with the control cells. Moreover, rhaponticin treatment improves in chemical assays and also the histopathological alteration of lung tissues. The present findings provide evidence about the therapeutic potentials of rhaponticin against BaP triggered lung tumorigenesis. 相似文献
950.
B. Jayashree Y. S. Bibin D. Prabhu C. S. Shanthirani K. Gokulakrishnan B. S. Lakshmi V. Mohan M. Balasubramanyam 《Molecular and cellular biochemistry》2014,388(1-2):203-210
Emerging data indicate that gut-derived endotoxin (metabolic endotoxemia) may contribute to low-grade systemic inflammation in insulin-resistant states. Specific gut bacteria seem to serve as lipopolysaccharide (LPS) sources and several reports claim a role for increased intestinal permeability in the genesis of metabolic disorders. Therefore, we investigated the serum levels of LPS and zonulin (ZO-1, a marker of gut permeability) along with systemic levels of tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) in patients with type 2 diabetes mellitus (T2DM) compared to control subjects. Study subjects were recruited from the Chennai Urban Rural Epidemiology Study [CURES], Chennai, India. Study group (n = 45 each) comprised of a) subjects with normal glucose tolerance (NGT) and (b) patients with T2DM. LPS, ZO-1, TNF-α, and IL-6 levels were measured by ELISA. Serum levels of LPS [p < 0.05], LPS activity [p < 0.001], ZO-1 [p < 0.001], TNFα [p < 0.001], and IL-6 [p < 0.001] were significantly increased in patients with T2DM compared to control subjects. Pearson correlation analysis revealed that LPS activity was significantly and positively correlated with ZO-1, fasting plasma glucose, 2 h post glucose, HbA1c, serum triglycerides, TNF-α, IL-6, and negatively correlated with HDL cholesterol. Regression analysis showed that increased LPS levels were significantly associated with type 2 diabetes [odds ratio (OR) 13.43, 95 % CI 1.998–18.9; p = 0.003]. In Asian Indians who are considered highly insulin resistant, the circulatory LPS levels, LPS activity, and ZO-1 were significantly increased in patients with type 2 diabetes and showed positive correlation with inflammatory markers and poor glycemic/lipid control. 相似文献