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121.
Hetal Damani Shah Dhananjaya Saranath Soma Das Prashant Kharkar Anjali Karande 《Journal of cellular biochemistry》2019,120(4):5519-5530
H-Ras oncogene plays a critical role in the transformation of normal cells to a malignant phenotype through constitutive activation of the GTP bound protein leading to uncontrolled cell proliferation in several human cancers. Thus, H-Ras oncoprotein serves as an excellent target for anticancer drug discovery. To identify novel H-Ras inhibitors, we performed structure-based virtual screening of the Maybridge HitFinder™ library using Schrodinger suite. Thirty ligands from the chemical library were identified as they showed preferential in silico binding initially to H-Ras proteins with Gly12Val, Gly13Asp, and Gly12Val-Gly13Asp mutations. Absorption, distribution, metabolism, excretion, and toxicity profile confirmed drug-like properties of the compounds. Three representative molecules were tested for antiproliferative effect on T24 urinary bladder carcinoma cell line, MCF-7 breast cancer cell line and HDF-7 normal dermal fibroblast cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Two compounds (Cmpds) showed antiproliferative activity exclusively in the cancer cell lines with minimal effect on the control HDF-7 cells. The effect of compound treatment on cell cycle progression, assessed by propidium iodide (PI) staining, depicted increased arrest of T24 cell line in the sub G1 phase. Further, Annexin-V PI dual staining and pan caspase inhibitor Z-VAD-fmk indicated caspase-dependent apoptotic activity of Cmpds 1 and 3. Our findings demonstrate caspase-dependent apoptotic activity of Cmpds 1 and 3 selectively against Gly12Val mutated T24 cancer cell line implicating a potential for treatment of bladder cancer. We envisage that these molecules may be promising candidates with potential therapeutic value in H-Ras mutation-associated cancers. 相似文献
122.
Hazam Prakash Kishore Singh Anjali Chaudhary Nitin Ramakrishnan Vibin 《International journal of peptide research and therapeutics》2019,25(2):465-472
International Journal of Peptide Research and Therapeutics - Tuberculosis is one of the leading causes of death, with an annual mortality rate of 2 million. The present treatment regimen... 相似文献
123.
Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites
Doron Betel Anjali Koppal Phaedra Agius Chris Sander Christina Leslie 《Genome biology》2010,11(8):R90
mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains
a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation,
miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of
their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally
determined non-canonical and non-conserved sites. 相似文献
124.
Cytokinins in the different regions of Cuscuta reflexa Roxb. vine have been extracted and assayed using the Xanthium cotyledon bioassay with N6 -benzylaminopurine as the reference cytokinin. Maximum cytokinin level was found in the haustoria-bearing region with the gradient decreasing towards the apex. The cytokinin content of the apex was less than 1% of that in the whole haustorial region. Interestingly, the concave half of the vine contained about forty times more cytokinin in the haustorial region than the corresponding convex half. The high concentration of cytokinin or cytokinin-like substances in the haustoria-bearing site in Cuscuta might be due either to a high RNase activity in the region or translocation from the host to parasite or both. 相似文献
125.
Genome Sequence of Acinetobacter sp. Strain HA, Isolated from the Gut of the Polyphagous Insect Pest Helicoverpa armigera 总被引:1,自引:0,他引:1
J Malhotra A Dua A Saxena N Sangwan U Mukherjee N Pandey R Rajagopal P Khurana JP Khurana R Lal 《Journal of bacteriology》2012,194(18):5156
In this study, Acinetobacter sp. strain HA was isolated from the midgut of a fifth-instar larva of Helicoverpa armigera. Here, we report the draft genome sequence (3,125,085 bp) of this strain that consists of 102 contigs, 2,911 predicted coding sequences, and a G+C content of 41%. 相似文献
126.
Ralhan A Schöttle S Thurow C Iven T Feussner I Polle A Gatz C 《Plant physiology》2012,159(3):1192-1203
Verticillium longisporum is a soil-borne vascular pathogen that causes reduced shoot growth and early senescence in Arabidopsis (Arabidopsis thaliana). Here, we report that these disease symptoms are less pronounced in plants that lack the receptor of the plant defense hormone jasmonic acid (JA), CORONATINE INSENSITIVE1 (COI1). Initial colonization of the roots was comparable in wild-type and coi1 plants, and fungal DNA accumulated to almost similar levels in petioles of wild-type and coi1 plants at 10 d post infection. Completion of the fungal life cycle was impaired in coi1, as indicated by the reduced number of plants with microsclerotia, which are detected on dead plant material at late stages of the disease. Contrary to the expectation that the hormone receptor mutant coi1 should display the same phenotype as the corresponding hormone biosynthesis mutant delayed dehiscence2 (dde2), dde2 plants developed wild-type-like disease symptoms. Marker genes of the JA and the JA/ethylene defense pathway were induced in petioles of wild-type plants but not in petioles of dde2 plants, indicating that fungal compounds that would activate the known COI1-dependent signal transduction chain were absent. Grafting experiments revealed that the susceptibility-enhancing COI1 function acts in the roots. Moreover, we show that the coi1-mediated tolerance is not due to the hyperactivation of the salicylic acid pathway. Together, our results have unraveled a novel COI1 function in the roots that acts independently from JA-isoleucine or any JA-isoleucine mimic. This COI1 activity is required for a yet unknown root-to-shoot signaling process that enables V. longisporum to elicit disease symptoms in Arabidopsis. 相似文献
127.
Our previous investigation reported the beneficial effect of pre-sowing magnetic treatment for improving germination parameters and biomass accumulation in soybean. In this study, soybean seeds treated with static magnetic fields of 150 and 200 mT for 1 h were evaluated for reactive oxygen species (ROS) and activity of antioxidant enzymes. Superoxide and hydroxyl radicals were measured in embryos and hypocotyls of germinating seeds by electron paramagnetic resonance spectroscopy and kinetics of superoxide production; hydrogen peroxide and antioxidant activities were estimated spectrophotometrically. Magnetic field treatment resulted in enhanced production of ROS mediated by cell wall peroxidase while ascorbic acid content, superoxide dismutase and ascorbate peroxidase activity decreased in the hypocotyl of germinating seeds. An increase in the cytosolic peroxidase activity indicated that this antioxidant enzyme had a vital role in scavenging the increased H(2)O(2) produced in seedlings from the magnetically treated seeds. Hence, these studies contribute to our first report on the biochemical basis of enhanced germination and seedling growth in magnetically treated seeds of soybean in relation to increased production of ROS. 相似文献
128.
Green tea (C. sinensis) extract (GTE) dose dependently produced reversal of despair in normal, reserpinised and diabetic mice, thereby demonstrating an antidepressant effect. Although the exact mechanism is yet to be explored, the possible inhibition of catechol-o-methyl transferase and monoamine oxidase enzymes may be responsible for antidepressant activity of GTE. 相似文献
129.
Ankyrin repeat, one of the most widely existing protein motifs in nature, consists of 30-34 amino acid residues and exclusively functions to mediate protein-protein interactions, some of which are directly involved in the development of human cancer and other diseases. Each ankyrin repeat exhibits a helix-turn-helix conformation, and strings of such tandem repeats are packed in a nearly linear array to form helix-turn-helix bundles with relatively flexible loops. The global structure of an ankyrin repeat protein is mainly stabilized by intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The repetitive and elongated nature of ankyrin repeat proteins provides the molecular bases of the unique characteristics of ankyrin repeat proteins in protein stability, folding and unfolding, and binding specificity. Recent studies have demonstrated that ankyrin repeat proteins do not recognize specific sequences, and interacting residues are discontinuously dispersed into the whole molecules of both the ankyrin repeat protein and its partner. In addition, the availability of thousands of ankyrin repeat sequences has made it feasible to use rational design to modify the specificity and stability of physiologically important ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel functions through combinatorial chemistry approaches. 相似文献
130.
Asif SM Asad A Faizan A Anjali MS Arvind A Neelesh K Hirdesh K Sanjay K 《Bioinformation》2009,4(6):245-248
Mycobacterium tuberculosis is the causative agent of the disease, tuberculosis and H37Rv is the most studied clinical strain. We use comparative genome analysis of Mycobacterium tuberculosis H37Rv and human for the identification of potential targets dataset. We used DEG (Database of Essential Genes) to identify essential genes in the H37Rv strain. The analysis shows that 628 of the 3989 genes in Mycobacterium tuberculosis H37Rv were found to be essential of which 324 genes lack similarity to the human genome. Subsequently hypothetical proteins were removed through manual curation. This further resulted in a dataset of 135 proteins with essential function and no homology to human. 相似文献