342 research outputs found
Nucleic Acid Targeted Therapy: G4 Oligonucleotides Downregulate HRAS in Bladder Cancer Cells through a Decoy Mechanism
No full textIn a previous study we have demonstrated that two neighboring G-quadruplexes, hras-1 and hras-2, located immediately upstream of the major transcription start site of HRAS, bind MAZ, a nuclear factor that activates transcription (Cogoi, S.; et al. Nucl. Acid Res. 2014, 42, 8379). For the present study we have designed G4 oligonucleotides with anthraquinone insertions and locked nucleic acids (LNA) modifications mimicking quadruplex hras-1. Luciferase, qRT-PCR, and Western blot data demonstrate that these constructs efficiently down regulate HRAS in T24 bladder cancer cells. The inhibitory efficiency of the G4 oligonucleotides correlates with their nuclease resistance in the cell environment. By chromatin immunoprecipitation we show that the association of MAZ to the HRAS promoter is strongly attenuated by the designed G4 oligonucleotides, thus suggesting that these constructs behave with a decoy mechanism
A half-century of metal and metalloid-containing polymers
No full textAlaa S. Abd-El-Aziz ... [et al.]; Includes bibliographical references and indexes.; Editor, Alaa S. Abd-El-Aziz, is currently President of the University of Prince Edward Island.Source type: Electronic(1
Dibenzyl ferrocene-1,1′-dicarboxylate
No full textIn the title compound, [Fe(C13H11O2)2], there are markedly different orientations of the two phenylmethoxycarbonyl substituents [O—C—C—C torsion angles = 84.5 (3) and 139.6 (2)°]. These orientations are mediated by a number of intermolecular C—H...O interactions, which result in a one-dimensional hydrogen-bonded network of molecules
A modified α-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis
No full texthttp://dx.doi.org/10.13039/501100000774 Newcastle Universityhttp://dx.doi.org/10.13039/100010036 Teesside Universityhttp://dx.doi.org/10.13039/501100002283 Alzheimer's Research U
A Novel Quinazoline Inhibits Hsp90 Protein, EGFR and Induces Apoptosis in Leukemia Cells
No full textThe objective of the first part of this study was to investigate the Hsp90 protein possible activ ity of a novel quinazoline Her2/ EGFR inhibitor (Co mpound No. 1: 4-(2-(4-Oxo-2-thio xo-1,4-d ihydroquinazolin-3(2H)yl)ethyl)benzenesulfonamide) p reviously synthesized by a collaborating group. Heat shock protein 90 (Hsp90) has a central ro le in regulation of several client proteins involved in cancers [1,2]. Several Hsp90 inhibitors of the natural or synthetic origin d isplayed potent anticancer activity [3,4]. Accordingly, Hsp90 emerged as an attractive target in the design of anticancer agents. To evaluate the binding mode of compound No. 1 into the ATPase site of Hsp90, a co mparative mo lecular docking study was performed using AutoDock 4.2. The results of this studywas compared with that of the co-crystallized ligand (ATI-13387X, Onalespib). The energy minimization process of the chemical structures of No. 1 was done following our previous report [5]. The results of the docking study revealed that No. 1 fit n icely into the ATPase site, and it displayed a binding free energy (Gb) of-7.21 kcal/ mo l and inhibition constant (Ki) of 5.19 μM to Hsp90, co mpared to Gb of-7.90 kcal/ mol and Ki of 1.62 μM for ATI-13387X. Furthermore, to confirm this result, the surface plasmon resonance (SPR) was devised to test the Hsp90 inhibition activity of No.1, wh ich was 51 nM co mpared to Rad icico l and 17AA G (1.8 nM, and 360 nM; respectively). Overall, co mpound No. 1 exh ibited pro mising Hsp90 inhib iting activity. The second part of the study focused on the effect of No. 1, Dinaciclib and their co mbinationsin HL-60 leukemia cells. The comb ination showed synergistic EGFR inhib ition effect in HL-60 cells. Moreover, No. 1, Dinaciclib and their combination caused a significant increase in the Sub-G1 co mpared to control and doxorubicin (24h), at the expense of S and G2/M cell cycle phases. Cyclin D3, was consequently inhibited by each of the two drugs, and synergistically by their comb ination in HL-60 cells. Furthermore, each of the two drugs downregulated Survivin, wh ich was synergistically inhib ited by the co mbination. In conclusion, co mpound No.1, Dinaciclib and their comb inations showed synergestic EGFR inhibit ion; and pro-apoptoticeffect in HL-60 cells.This project was funded by the deanship of scientific research, Umm Alqura University, KSA (DSR: 15-M ED-3-1-0060). Keywords: Novel quinazoline EGFR inhi bi tor, Hs p90 protein, Leukemi a cells
Induction of preferential helical screw senses in optically inactive polysilanes via chiral solvation
No full textCommunication: Two optically active solvents were synthesised, (S)-(-)-2-methyl-1-propoxybutane and (S)-(-)-(2-methylbutoxymethyl)benzene. The main chain conformations of poly(methylphenylsilane) and poly(hexylmethylsilane) in these solvents were investigated using optical UV-visible and circular dichroism spectroscopy. It was observed that dissolving these inherently achiral polysilanes in optically active solvent induces the polymer chains to adopt preferred helical screw senses. This is the first example of induction of optical activity in conjugated polymers through chiral solvation
Innovative approach to the synthesis of sulfides and their corresponding sulfones.
No full textNucleophilic arom. substitution (SnAr) of cyclopentadienyliron-arene complexes with various aliph. or arom. dithiols followed by oxidn. and/or photolysis is presented as a viable route to the prepn. of the corresponding bis(sulfides) and bis(sulfones) in yields of 70-96%. The photochem. reaction of iron complexes I (R = H, alkyl, etc.; X = O, S; Cp = cyclopentadienyl) gave the sulfides II (same R, X)
Properties of SnO2 thin films deposited by chemical spray pyrolysis using different precursor solutions
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