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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 Aug 01 2024
Journal Name
Baghdad Science Journal
APR-246 enhances the anticancer effect of doxorubicin against p53-mutant AsPC-1 pancreatic cancer cells
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سرطان البنكرياس هو مرض ذو معدل وفيات مرتفع، ولا يزال التشخيص المبكر لسرطان البنكرياس يمثل تحديًا. يظل معدل البقاء النسبي لمدة 5 سنوات أقل من 8%، والاستراتيجيات العلاجية غير فعالة في زيادة معدلات بقاء المريض على قيد الحياة. في خلايا سرطان البنكرياس، ارتبطت مقاومة العلاج بالتغيرات الجينية التي تؤدي إلى ظهور مسارات خلوية شاذة؛ ولذلك، هناك ما يبرر ايجاد استراتيجيات جديدة لعلاج هذا المرض. هنا، سعينا لاستكشاف

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Publication Date
Wed Jun 01 2016
Journal Name
Ieee Transactions On Neural Systems And Rehabilitation Engineering
Improving the Performance Against Force Variation of EMG Controlled Multifunctional Upper-Limb Prostheses for Transradial Amputees
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Publication Date
Wed Dec 01 2021
Journal Name
Baghdad Science Journal
Studying the Photodegradation of Congo Red Dye from Aqueous Solutions Using Bimetallic Au–Pd/TiO2 Photocatalyst
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In this study, the photodegradation of Congo red dye (CR) in aqueous solution was investigated using Au-Pd/TiO2 as photocatalyst. The concentration of dye, dosage of photocatalyst, amount of H2O2, pH of the medium and temperature were examined to find the optimum values of these parameters. It has been found that 28 ppm was the best dye concentration. The optimum amount of photocatalyst was 0.09 g/75 mL of dye solution when the degradation percent was ~ 96 % after irradiation time of 12 hours, while the best amount of hydrogen peroxide was 7μl/75 mL of dye solution at degradation percent ~97 % after irradiation time of 10 hours, whereas pH 5 was the best value to carry out the reaction at the highest degradation percent. In additio

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Publication Date
Mon Dec 01 2025
Journal Name
Applied Thermal Engineering
Efficient thermal management of PVT systems via water-PCM hybridization: New design with optimized geometrical configuration
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Publication Date
Wed May 10 2017
Journal Name
Journal Of The College Of Languages (jcl)
Procedimientos de traducción de los nombres propios del árabe al español: Fundamentos y Aplicaciones Procedures for translating proper noun from Arabic into Spanish: Fundamentals and Applications
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Los nombres propios nombran a un ser o a un objeto, distinguiéndolo de los demás seres de su misma clase, se escriben siempre con letra mayúscula a principio de palabra. Los lingüistas hacen mayor hincapié en las divergencias de referencia, entre nombres propios y nombres comunes. Así, suele decirse que el sustantivo propio no tiene como referente ningún concepto. El asunto de la traducción  de los nombres propios parecería una cuestión de gusto personal del traductor pero vemos también que en algunas épocas es más frecuente traducirlos, y en otras, por el contrario, se prefiere dejar esos nombres en su forma original, tal vez con algunas adaptaciones ortográficas. Parecería enton­ces cuestión de modas. Pero, eviden

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Publication Date
Sat Dec 31 2016
Journal Name
Al-kindy College Medical Journal
Dorsal plication during penile orthoplasty with and without neurovascular bundle mobilizationA comparative clinical trial conducted At Ghazy Al-Hariri teaching hospital for surgical specialties (2013 –2015)
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Background: Dorsal plication on each side of the penis at the 2 and 10-o’clock positions had been a mainstay for correction of ventral penile curvature. However, because only the 12-o’clock position proved to be a nerve-free zone, dorsal plication at the 12-o’clock position can be advocated.

Objectives: To evaluate tunica albuginea plication with and without neurovascular bundle mobilization in patients with ventral penile curvature. Type of the study: A prospective study.

Methods: A 34 patients with a mean age of (4.8 ± 0.54) years, Who still

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Publication Date
Fri Sep 30 2011
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Vapor-Liquid-Liquid Equilibrium (VLLE) Data for the Systems Ethyl acetate + Water, Toluene + Water and Toluene + Ethyl acetate + Water at 101.3 kPa. Using Modified Equilibrium Still
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Isobaric Vapor-Liquid-Liquid equilibrium data for the binary systems ethyl acetate + water, toluene + water and the ternary system toluene + ethyl acetate + water were determined by a modified equilibrium still, the still consisted of a boiling and a condensation sections supplied with mixers that helped to correct the composition of the recycled condensed liquid and the boiling temperature readings in the condensation and boiling sections respectively. The VLLE data where predicted and correlated using the Peng-Robinson Equation of State in the vapor phase and one of the activity coefficient models Wilson, NRTL, UNIQUAC and the UNIFAC in the liquid phase and also were correlated using the Peng-Robinson Equation of State in both the vapo

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Publication Date
Thu Jun 02 2011
Journal Name
Ibn Al-haithem Journal For Pure And Applied Sciences
On modified pr-test double stage shrinkage estimators for estimate the parameters of simple linear regression model
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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Impact of Glycated Haemoglobin on salivary glucose among type 1 diabetic mellitus patients aged 18-22 years
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Background: Diabetes mellitus consists of a group of diseases characterized by abnormally high blood glucose levels. Glycated haemoglobin (HbA1c) is a form of haemoglobin used to identify the average concentration of plasma glucose over prolonged periods of time. It is formed in a non-enzymatic pathway by normal exposure of hemoglobin to high levels of plasma glucose, The main alterations observed in the saliva of Type 1 diabetic patients are hyposalivation and alteration in its composition, particularly those related to the levels of glucose. The aim of the present study was to assess the effect of Glycated haemoglobin level on the level of salivary glucose which may have an effect on oral health condition. Materials and methods

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Publication Date
Mon Mar 18 2019
Journal Name
Civil Engineering Journal
Circularization Technique for Strengthening of Plain Concrete Short Square Columns Subjected to a Uniaxial Compression Compressive Pressure
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This paper presents an experimental study for strengthening existing columns against axial compressive loads. The objective of this work is to study the behavior of concrete square columns strengthening with circulation technique. In Iraq, there are significantly more reinforced rectangular and square columns than reinforced circular columns in reinforced concrete buildings. Moreover, early research studies indicated that strengthening of rectangular or square columns using wraps of CFRP (Carbon Fiber Reinforced Polymer) provided rather little enhancement to their load-carrying capacity. In this paper, shape modification technique was performed to modify the shape (cross section) of the columns from square columns into circular colu

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