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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Thu Sep 01 2016
Journal Name
Saudi Journal Of Pathology And Microbiology
Synthesis, Characterization and Antibacterial Activities of Mixed Ligand Complexes of Symmetrical Schiff Base and 8-Hydroxyquinoline with Zn(II), Cd(II) and Hg(II)
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The current work reports a new Schiff base [N1-benzylidenebenezene-1,2-diamine(L) = C20H16N2] has been synthesized from benzaldehyde (C6H5CHO) and O- aminoaniline (O-C6H4(NH2)2. Metal mixed ligand complexes of the Schiff base were prepared from chloride salts of Zn(II), Cd(II) and Hg(II) in ethanol and 8-hydroxyquinoline(8HQ)(C9H7NO) containing sodium hydroxide. All the complexes were characterized on the basis of their; FT-IR and U.V spectra, melting point, molar conductance, and determination of the percentage of the metal in the complexes by flame (AAS). In the all complexes, (8HQ) behaves as a bidentate ligand as primary ligand through –-OH phenolic group and –N groups of pyridine group. Also, the prepared ligand (L) was bidentate i

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Publication Date
Mon Jun 01 2009
Journal Name
Al-khwarizmi Engineering Journal
Breast Tumor Diagnosis Using Diode Laser in Near Infrared Region
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In the last years, new non-invasively laser methods were used to detect breast tumors for pre- and postmenopausal females. The methods based on using laser radiation are safer than the other daily used methods for breast tumor detection like X-ray mammography, CT-scanner, and nuclear medicine.  

      One of these new methods is called FDPM (Frequency Domain Photon Migration). It is based on the modulation of laser beam by variable frequency sinusoidal waves. The modulated laser radiations illuminate the breast tissue and received from opposite side.

      In this paper the amplitude and the phase shift of the received signal were calculated according to the orig

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Publication Date
Thu Jan 01 2015
Journal Name
Chemical And Process Engineering Research
SYNTHESIS, Spectroscopic Characterization and Evaluation (Antibacterial & (GOT, G pT) Enzyme )Activity of Mixed Ligand Complexes of M(II) with Amino Acid (L-Asparagine) and Schiff Bases Derived from (Sulfamethoxazo Drug with 2,4Dimethoxybenzaldehyde)
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The research includes the synthesis and identification of the mixed ligands complexes of M 2 Ions in general composition ,[M(Leu) 2 (SMX)] Where L leucine (C 6 H 13 NO 2 )symbolized (LeuH) as a primary ligand and Sulfamethoxazole C 10 H 11 N 3 O 3 S) symbolized (SMX)) as a secondary ligand . The ligands and the metal chlorides were brought in to reaction at room temperature in(v/v) ethanol /water as solvent containing NaOH. The reaction required the following [(metal: 2(Na Leu --): (SMX )] molar ratios with M(II) ions, Were M (  Mn ( II),Co (II),Ni(II),Cu( II),Zn (II),Cd(II)and Hg( The UV Vis and magnetic moment data revealed an octahedral geometry around M(II), The conductivity data show a non electrolytic nature of the complexes . The

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Efficacy, safety and Cardiovascular Disease Risk Lowering Ability of ACE Inhibitors, B-Blockers and Combination Antihypertensive Drug Regimes in Iraq
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Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular diseases. It is defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. The aim of this study was to compare the efficacy, safety and cardiovascular disease risk lowering ability, of three antihypertensive drug regimens.

A retrospective study was carried out on 66 hypertensive patients, divided in to three groups based on their antihypertensive drug regimens (ACE inhibitors, β-blockers treated and combination antihypertensive therapy, the combination therapy consist of two or more of the following antihypertensive drugs ACE inhibitor di

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Publication Date
Sat Sep 30 2023
Journal Name
Romanian Journal Of Rheumatology
Association between genetic polymorphism in tumor necrosis factor-alpha gene and adverse effects of etanercept in rheumatoid arthritis patients
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Background. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymo

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Publication Date
Mon Jan 01 2018
Journal Name
Rehabend
Prediction of impact force-time history in sandy soils
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Publication Date
Fri Jun 24 2022
Journal Name
Iraqi Journal Of Science
Theoretical Study of New Derivative of Cefotaxime-Amic Acid as a Corrosion Inhibitor
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PM3 and DFT quantum mechanical calculations were employed to give further
insight into the inhibition efficiency of the newly prepared cefotaxime amic acid
derivative. The calculated physical properties and quantum chemical parameters
correlated to the inhibition efficiency such as EHOMO (highest occupied molecular
orbital energy), ELUMO (lowest unoccupied molecular orbital energy), the energy gap
(ΔE(HOMO-LUMO)), hardness (η), softness (S), dipole moment (μ), electron affinity
(EA), ionization potential (IE) and active site absorption..…etc., all studied and
discussed at equilibrium geometry in the gas phase and at its right symmetry (C1).
Experimentally the newly prepared cefotaxime derivative could be abso

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Publication Date
Mon Jan 28 2019
Journal Name
Journal Of The College Of Education For Women
Relation Ship and Effect Of Jet Stream in Anti-Ciyclone in Influencing The Climate Of Iraq
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This study aimed to statement jet stream and its impact in the anti-cyclone affecting the climate of Iraq. Through the use of simple correlation coefficient ( Pearson ) that there is a very strong relationship between high- Siberian and both of the jet stream especially during the winter or over the stations of North . Therefore we, observe the relationship be significant in most of the winter months , spring and autumn . Statistically significant , but are different between station and another station , while the study come to another Anti-ciyclon have a real ,significant and statistically relationship corrclation . But this relationship is less than which found in are much less it with the Siberian high , it depends on the type of stat

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Publication Date
Wed Jan 11 2023
Journal Name
Healthcare
Short-Term (4 Day) Effects of Oral Rinsing with Miswak and Green Tea on Gingival Crevicular Fluid Flow and IL-1β Levels: A Pilot Study
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Despite the antiplaque effect of mouth-rinsing with a combination composed of miswak (Salvadora persica L.) and green tea (Camellia sinensis var. assamica) extracts, no data are available regarding its effect on gingival tissue at the molecular level. This pilot study aimed to assess the effect of oral rinsing with this combination on gingival crevicular fluid (GCF) flow and IL-1β levels. Ten subjects rinsed with either the combination, 0.12% chlorhexidine gluconate (CHX) or distilled water without toothbrushing for 4 days after receiving baseline polishing. GCF IL-1β concentration, influx, resting volume and plaque quantity were measured at baseline and after 4 days for each intervention. No significant differences in GCF flow or

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Publication Date
Sat May 13 2023
Journal Name
Journal Of Population Therapeutics And Clinical Pharmacology
Synthesis, Characterization of Schiff's and Mannich bases of 5-Fluoroisatin and Preliminary Antimicrobial Evaluation
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With the aim of developing potential antimicrobials, a series of new 5-fluoroisatin derivatives incorporated with different secondary amines (piperidine, morpholine, pyrrolidine, dimethylamine, and diphenylamine) for monomer, and (piperazine) in case of dimer Mannich bases, separately in presence of formaldehyde to obtain Mannich bases of 5-fluoroisatin derivatives, which then each Mannich derivatives reacts with phenylhydrazine to form Schiff bases as final products. The resulting compounds were characterized by two spectroscopic analyses; (Fourier- transform infrared) FT-IR and proton nuclear magnetic resonance spectroscopy (¹H-NMR). In addition, the in vitro antibacterial and antifungal activities were tested against some human pathogen

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