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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
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Stability of Cefamandol and Ceftazidime with Clavulanic Acid Against Extended Spectrum ?- Lactamase
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The aim of this study is to evaluate in-vitro activity of Cefamandol (Cfm) and Ceftazidime (Cfz), in combination with Clavulanic acid (CA) against ten complicated multiresistant uropathogenic E.coli .One hundred clinical strains were isolated from patients with chronic urinary tract infections (UTIs), these isolates were identified by the Api identification systems. The antimicrobial susceptibility tests were determined by Kirby-Bauer method, all of them were sensitive to Imipenem (Imp). Ten strains were chosen for the present study, they were resistant to Ampicillin (Amp), Amoxicillin (Amo), Carbenicillin (Cb), Ticarcillin (Tic), Azlocillin (Azl), Amoxicillin\ Potassium Clavulanate {Augmentin(Amc)}, (Amo\CA), Ticarcillin\ Potas

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Publication Date
Wed Jun 24 2020
Journal Name
Systematic Reviews In Pharmacy
Studies on the Photostability of Polystyrene Films with New Metals Complex of 1, 2, 4-triazole-3-thione Derivate
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The new complexes including Cu(II), Co(II), Ni(II), Pt(IV), and Pd(II) metals with 4,4'-(((1E,1'E)-1,4-phenylenebis(methaneylylidene))bis(azaneylylidene))bis(5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thione) have been synthesized of utilizing us polystyrene (PS) photostability. The supplement (0,5 w / v%) was for the production of polystyrene ( PS) in the form of tetrahydrofuran (THF). Polystyrene films were exposing irradiation (250 – 380 nm) absorption light intensity of 6.02 x 10-9 ein dm-3 s-1 at room temperature, through the changes that occur to each of viscosity average molecular weight (Mv), main chain scission (S), degree of polymerization (DPn), weight loss %, hydroxyl index (lOH), carbonyl index (ICo) determined the photo stabiliz

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effect of COX-2 Inhibitors Selectivity on Lipid Profile in Hyperlipidemic and Normolipidemic Type 2 Diabetics
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Development of NSAIDS based on inhibiting cyclooxygenase activity. However, the different physiological consequences arrised by appearance of new drugs with different selectivity to COX-2 enzyme upon their administration with their relevant affects on some cardiovascular risk factors. To study the potential effects of relatively  diclofenac and highly specific  celecoxib COX-2 inhibitors on lipid profile and serum C-reactive protein in type 2 diabetes, whom have hyperlipidemia to be compared by their effects with normolipidemic patients. A total number of 34 type 2 diabetics (14 normolipidemics and 20 hyperlipidemics) treated with either diclofenac 100mg/day or celecoxib 200mg/day for eight weeks. Analysis  of results indi

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Publication Date
Mon Aug 30 2021
Journal Name
Al-kindy College Medical Journal
Diagnostic Evaluation of Uterine Artery Doppler Imaging for the Prediction of Early Abnormal Pregnancy
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Objective: to assess the predictive value of Doppler imaging of the uterine artery in the identification of early intrauterine abnormal pregnancy as compared to a normal intrauterine pregnancy. Subjects and methods: one hundred and twenty pregnant ladies, at their 6-12 weeks of gestation, with a singleton pregnancy were included in this population-based case-control study. Thirty women with a missed miscarriage, 30 with hydatidiform mole, 30 with a blighted ovum, and 30 as a control group, without risk factors, underwent Doppler interrogation of the uterine arteries. Resistive index (RI), pulsatility index (PI), and the systolic/diastolic ratio (S/D) were measured for both sides. The t-test, or ANOVA test when appropriate, was

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Publication Date
Mon Aug 30 2021
Journal Name
Al-kindy College Medical Journal
Diagnostic Evaluation of Uterine Artery Doppler Imaging for the Prediction of Early Abnormal Pregnancy
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Objective: to assess the predictive value of Doppler imaging of the uterine artery in the identification of early intrauterine abnormal pregnancy as compared to a normal intrauterine pregnancy.

Subjects and methods: one hundred and twenty pregnant ladies, at their 6-12 weeks of gestation, with a singleton pregnancy were included in this population-based case-control study. Thirty women with a missed miscarriage, 30 with hydatidiform mole, 30 with a blighted ovum, and 30 as a control group, without risk factors, underwent Doppler interrogation of the uterine arteries. Resistive index (RI), pulsatility index (PI), and the systolic/diastolic ratio (S/D) were measured for both sides. The t-test, or ANOVA test when a

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Publication Date
Wed Jan 01 2020
Journal Name
Journal Of Clinical And Experimental Dentistry
In vitro bond strengths post thermal and fatigue load cycling of sapphire brackets bonded with self-etch primer and evaluation of enamel damage
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Background: This in vitro study compares a self-etch primer (SEP) to an etch-and-rinse (EaR) for bonding sapphire brackets by evaluation of the enamel etch-pattern, shear bond strength, amount of remnant adhesive and enamel surface damage following thermal and fatigue cyclic loading. Material and Methods: Ceramic (sapphire) brackets were bonded to 80 extracted human premolars using two enamel etching protocols: conventional EaR using 37% phosphoric acid (PA) gel (control), and a SEP (Transbond Plus). Each group was subdivided into two subgroups (n=20 teeth) according to the time of bracket debonding: after 24 h water storage or following 5000 thermo-cycles plus 5000 cycles fatigue loading, to determine the shear bond strength (SBS), adhesiv

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Publication Date
Thu Jun 30 2016
Journal Name
Al-kindy College Medical Journal
Impact of short term intervention on mother knowledge, attitude and practice to improve oral hygiene of their children aged(4-7) Years Old in Al-Shaab Area - Baghdad City
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Background: Mothers are considered as the key role in effect on child's dental behavior. So it is important to involve her in oral health promotion program to prevent early childhood dental caries from occurring in early age. Objectives: To identify the knowledge, practice and attitude of mothers about the oral health of their children. And to measure the change in oral hygiene of children aged (4-7) years old after one month of interventional program on their mothers. Type of study: Non-randomized interventional.Methods: Non-randomized interventional study for one month in Al Shaab area in Baghdad to 65 mothers who have children aged (4-7) years .A modified administrated questionnaire is given to assess mothers’ knowledge, practice an

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of preheating on micro leakage of Class II composites Restoration (A comparative in vitro study)
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Background: The aim of this in vitro study was to evaluate and compare the effect of preheating microleakage among three different filler size composites which include Filtektm Z250 micro hybrid, Z250xt Nano hybrid and nanocomposite Z350xt.  in Class II cavity preparation .

Materials and methods: sixty maxillary first premolars were prepared with class II cavities. Samples were divided into three groups according to material used    group A (FiltekZ250 micro hybrid). Group B(Z250xt Nano hybrid). Group C (nanocomposite Z350xt)and each group divided into two subgroups of ten teeth according to temperature of  composite:

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Pharmaceutical Negative Results
Phytocompound of pure thymol inhibit COVID-19 by binding to ACE2 receptor: In silico approach
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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)
Study the Effect of Folic Acid as A supplement on Selected Oxidative Stress and Biochemical Parameters in First Trimester of Pregnancy
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Folic acid modulates several disorders in humans, pregnancy mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress.Transitional metals, especially iron, which are particularly abundant in the placenta, are important in the production of free radicals. Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. In the present study we investigated the effect of regular and irregular administered folic acid in the first and second trimester of pregnancy to be compared with non-pregnant women ,and also the effect of regular and irregular using of folic acid  supplement on  oxidative stress parameters an

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