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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
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Role of Ginkgo biloba Extract as Monotherapy in Improving the Outcomes of Patients with Metabolic Syndrome: A Pilot Comparative Study with Metformin
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The present study evaluates the effects of Ginkgo biloba extract as monotherapy on the glycemic status, insulin resistance (IR), body mass index (BMI), and visceral adiposity index (VAI), in addition to the inflammatory markers, oxidative status and leptin level in patients with metabolic syndrome in comparison with metformin.

The study is a randomized, double-blind pilot study conducted during the period May to September, 2020. Fifty patients were recruited in the study and they were allocated into two groups (25 per each group): Ginkgo biloba and Metformin groups, they received (120 mg Ginkgo biloba extract/ capsule) and (500 mg Metformin/ capsule) respectively; orally as a single dose for 90 days. Blood samples were taken at z

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Publication Date
Wed Oct 01 2014
Journal Name
Iosr Journal Of Mathematics
Flow through an Oscillating Rectangular Duct for Generalized Oldroyd-B Fluid with Fractional Derivatives
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The analytic solution for the unsteady flow of generalized Oldroyd- B fluid on oscillating rectangular duct is studied. In the absence of the frequency of oscillations, we obtain the problem for the flow of generalized Oldroyd- B fluid in a duct of rectangular cross- section moving parallel to its length. The problem is solved by applying the double finite Fourier sine and discrete Laplace transforms. The solutions for the generalized Maxwell fluids and the ordinary Maxwell fluid appear as limiting cases of the solutions obtained here. Finally, the effect of material parameters on the velocity profile spotlighted by means of the graphical illustrations

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Publication Date
Tue Dec 30 2014
Journal Name
Scholars Academic Journal Of Biosciences (sajb)
Prevalence and Evaluation of Antimicrobial Activity of Dodonaea viscosa Extract and Antibacterial Agents against salmonella Spp. Isolated from Poultry
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A total of 200 samples (180 fecal materials and 20 organ samples) were collected from (5 different poultry farms, 10 local poultry shops, 5 houses poultry, 5 Eggs stores shops and 5hand slaughters centers) in Ibb city, Yemen, 2014. According to morphological, cultural, as well as biochemical characterization and serological tests, 59(29.5%) isolates were identified as Salmonella spp. and all Salmonella isolates were categorized by serotype, which comprised of, 37(62.71%) Salmonella Typhimurium serovar, 21(35.59%). Salmonella Enteritidis serovar and 1(1.69%) Salmonella Heidlberg serovar. Antibiotic sensitivity test was done for bacterial isolates and the results showed there were clear differences in antibiotic resistant. Antimicrobial

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Publication Date
Thu Jul 16 2020
Journal Name
Polymer Bulletin
Fabrication and evaluation of structural, thermal, mechanical and optical behavior of epoxy–TEOS/MWCNTs composites for solar cell covering
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Publication Date
Thu Jun 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Formulation and Evaluation of High-Fat Pellet on Lipid Profiles and Body Mass Index of Male Wistar Rats
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This study aimed to explore the manufacture of high-fat pellets for obesity induction diets in male Wistar rats and determined its effect on lipid profiles and body mass index. It was an experimental laboratory method with a post-test randomized control group. Formulation of high-fat pellets (HFD) and physico-chemical characteristics of pellets were conducted in September 2019. This study used about 28 male Wistar white rats, two months old, and 150-200 g body weight. Rats were acclimatized for seven days, then divided into four groups: 7 rats were given a standard feed of Confeed PARS CP594 (P0), and three groups (P1, P2, P3) were given high-fat feed (HFD FII) 30 g/head/day. The result showed that the mean fat content of Formula II pell

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Publication Date
Sun Mar 15 2020
Journal Name
Journal Of The College Of Education For Women
Evaluation of Holy Quran & Islamic Education Curriculum of Second Intermediate Stage from Perspectives of Teachers & Supervisors of the Material:A Field Study conducted in the Directorates-General of Education in Baghdad Governorate: أشواق عبـد الحـسن عبـد
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Evaluation of “Holy Quran & Islamic Education” Curriculum for Second Intermediate Stage from Perspectives of Teachers & Supervisors of material A Field Study conducted in the Directorates-General of Education in Baghdad Governorate. It goes without saying that educational curricula for students of all stages of schooling are in bad need of reviewing, evaluation and revision. The Islamic education curriculum is no exception, since it is a basic subject that plays a role in developing the individual’s moral and conscientious aspects, promotes his/her inner discipline and helps establish coherence with the values system of the community to which he/she belongs.

Based on the foregoing, the evaluation process of

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Publication Date
Sun Aug 13 2017
Journal Name
Iraqi Journal Of Agricultural Sciences
EFFECT OF SUPPLEMENTING DIFFERENT LEVELS OF CONJUGATED LINOLEIC ACID (CLA) TO THE DIET ON PRODUCTIVE PERFORMANCE OF BROILER CHICKEN
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This study was carried out at Poultry Research Station, State Board of Agricultural Research, Ministry of Agriculture for the period from 27 September 2014 to 9 November 2014 to evaluate the Supplementation of different levels of Conjugated Linoleic Acid (CLA) on productive performance of broiler. Four hundred eighty chicks (Ross-308),one day old were randomly distributed to four dietary treatments for 42 days of age with 3 replicates/vtreatment (40 bird/replicate). Experimental treatments were as follow; T1 (Control diet) without supplement, while the treatment T2,T3 and T4  were Supplemented with 1, 1.5, 2 g CLA /kg diet  respectively. The results showed significant (P ≤ 0.05) increased in mean of body weight, weight gain, ave

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Publication Date
Wed Jun 29 2022
Journal Name
Journal Of The College Of Education For Women
Gender and Urban Studies as an Interactive Approach and Integrated Curriculum
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The integration of gender in urban studies is considered a goal and objective to build a society characterized by justice and equality. It further allows all its residents to enjoy the opportunities to live in a safe urban life. Based on the that, the limitations of the research and its field of interest related to the relationship between gender and urban studies have become clear. The insufficient knowledge in this regard considers gender as a concept that does not exist in itself, but rather overlaps and intersects with several concepts and studies, including urban studies. Thus, it has become necessary to adopt a descriptive methodology that helps reach a theoretical framework to explain the beginnings of such an interaction and inte

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Publication Date
Wed Mar 04 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of Autolougues Platelet Rich Fibrin Matrix on osseointegration of the titanium implant immunohistochemical evaluation for PDGF-I&IGF-A
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Background: Platelet-rich fibrin (PRF) is a simple, low cost and minimally invasive way to obtain a natural concentration of autologous growth factors and is currently being widely experimented in different fields of medicine for its ability to aid the regeneration of tissue with a low healing potential. Fields of application are sports medicine, orthopedics, dentistry, dermatology, ophthalmology, plastic and maxillofacial surgery, etc. The rationale for using platelets in so many fields for the treatment of different tissues is because PLTs constitute a reservoir of critical GFs and cytokines, which may govern and regulate the tissue healing process that is quite similar in all kinds of tissues. Materials and Methods: Screw titanium implan

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Publication Date
Thu Feb 15 2018
Journal Name
International Journal Of Architectural Heritage
Active use of panoramic mobile mapping systems for as built surveying and heritage documentation
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