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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
Sun Sep 16 2018
Journal Name
British Journal Of Educational Technology
Group tagging: Using video tagging to facilitate reflection on small group activities
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Collaborative learning in class‐based teaching presents a challenge for a tutor to ensure every group and individual student has the best learning experience. We present Group Tagging, a web application that supports reflection on collaborative, group‐based classroom activities. Group Tagging provides students with an opportunity to record important moments within the class‐based group work and enables reflection on and promotion of professional skills such as communication, collaboration and critical thinking. After class, students use the tagged clips to create short videos showcasing their group work activities, which can later be reviewed by the teacher. We report on a deployment of Group Tagging in an undergraduate Computing Scie

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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Anti-obesity effect of simvastatin and omega-3 and its combination on obese model male Wistar rats: Effect of simvastatin, omega-3 and their combination on UCP1
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      Strategies to reduce obesity have become main priority for many health institution and health staff around the world, as the prevalence of obesity has risen and exacerbated in most of the world mainly because of the modern life style which tend to be more sedentary with an increase eating unhealthy fast western food. Many years ago, the lipid-lowering drug simvastatin; and omega-3 were considered as a traditional lipid-lowering drug that have been well-documented to possess anti-inflammatory, cardioprotective and triglyceride-lowering properties; and their co-administration may demonstrate a complementary effect in lowering patients' triglycerides and total cholesterol to treat atherosclero

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
INVESTIGATION OF BENTONITE CLAY SURFACE AS A PHYSICAL ANTIDOTE IN ADSORPTION OF AMITRIPTYLINE-HCl, CHLORPROMAZINE-HCl AND CHLORDIAZEPOXIDE-HCl FROM SOLUTION
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A detailed study of adsorption from solution of amitriptyline-HCl, chlorpromazine-HCl and
chlordiazepoxide-HCl on bentonite clay surface has been performed at variable conditions of
temperature, pH and ionic strength. It is aimed in this work to explore the capability of this clay in
treatment of poisoning by the mentioned drugs if taken in quantities higher than the usual doses.
Quantities of drugs adsorbed have been determined by UV spectrophotometric technique. The
sequence of adsorption in neutral media at 37.5 CÙ’ followed the order:
Amitriptyline-HCl > chlorpromazine-HCl > chlordiazepoxide-HCl.
The results were discussed in the light of Langmuir and Freundich adsorption isotherms. The usual
basic th

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Publication Date
Fri Sep 30 2022
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Adsorption Isotherms and Isosteric Heat of Adsorption of Metal Organic Frameworks as Gas Storage for Liquefied Petroleum Gas Vehicle in Iraq
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   This research provides a novel technique for using metal organic frameworks (HKUST-1) as a gas storage system for liquefied petroleum gas (LPG) in Iraqi vehicles to avoid the drawbacks of the currently employed method of LPG gas storage. A low-cost adsorbent called HKUST-1 was prepared and characterized in this research to investigate its ability for propane storage at different temperatures (25, 30, 35, and 40 oC) and pressures of (1-7) bar. HKUST-1 was made using a hydrothermal method and characterized using powder X-ray diffraction, BET surface area, scanning electron microscopic (SEM), and Fourier Transforms infrared spectroscopy (FTIR). The HKUST-1 was produced using a hydrothermal technique and possesses a high crys

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Publication Date
Wed Jun 30 2021
Journal Name
College Of Islamic Sciences
the Employing Quranic studies in the social aspect: (The verses of Hudud, the limit of murder and theft as a model)
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Research Summary

Praise be to God, and may blessings and peace be upon the Messenger of God. As for:

The Noble Qur’an is the constitution of life, and a comprehensive educational approach that deals with individuals comprehensively, as it organizes worldly and eschatological life, and it is a curriculum concerned with organizing life starting with individuals and the family until the establishment of states, and from its comprehensiveness is reform, guidance and establishing boundaries. They have a disease in their hearts. They are exposed to this and are trying, by falsehood, to subjugate the Islamic world with man-made laws set by the West. Their aim is to distance people from

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Publication Date
Fri Nov 01 2019
Journal Name
Recent Technologies In Sustainable Materials Engineering
Evaluation of Tensile Strength and Durability of Microbial Cement Mortar
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Publication Date
Fri Jan 01 2021
Journal Name
Ieee Access
Total Dissolved Salt Prediction Using Neurocomputing Models: Case Study of Gypsum Soil Within Iraq Region
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Publication Date
Fri Dec 01 2017
Journal Name
2017 12th International Conference For Internet Technology And Secured Transactions (icitst)
A novel multimedia-forensic analysis tool (M-FAT)
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Publication Date
Sat Jan 01 2022
Journal Name
Intelligent Automation & Soft Computing
A Novel Classification Method with Cubic Spline Interpolation
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Publication Date
Wed Mar 15 2023
Journal Name
Bionatura
Cytotoxic potential activity of quercetin derivatives on MCF-7 breast cancer cell line
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Many previous investigations have found quercetin to be a powerful antioxidant and antitumor flavonoid, but its poor bioavailability has limited its use. This current study investigated the effects of two newly synthesized Quercetin Schiff bases containing 2-amino thiadiazole-5-thiol (Q1), and its benzyl derivatives (Q2) on MCF-7 human breast cancer cells. Cell viability and apoptosis were assessed to determine the toxic effects of Q1 and Q2. Cytotoxicity valuation showed that both compounds inhibited MCF-7 cell growth, and lactate dehydrogenase (LDH) activity increased in a dose-dependent aspect compared to the control group. Comet assay results observed that Q1 and Q2 induce more serious DNA damage than the control (untreated cell

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