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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
Fri Oct 01 2021
Journal Name
Journal Of Engineering
Critical Evaluation for Grading and Fineness Modulus of Concrete Sands used in Sulaymaniyah City-Iraq
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Fine aggregates used for concrete works in Sulaymaniyah city frequently fail to meet the standard requirements for gradation and fineness modulus in cement concrete. This paper aims to critically evaluate gradation, fineness modulus, and clay contents of various natural sands produced and used for concrete work in the region.  Sixteen field sand samples were collected from various sites in Darbandikhan (5 samples), Qalat Dizah (5 samples), Koysinjaq (5 samples), and Piramagroon (1 sample) confirming to ASTM D75. The field samples were parted into test specimens based on ASTM C702. Then, sieve analysis was carried out on the oven-dry test specimens in compliance with ASTM C136. The test results of fine aggregates wer

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Publication Date
Mon Jun 25 2018
Journal Name
Oriental Journal Of Chemistry
Advancement and Validation of new Derivatives Spectrophotometric Method for Individual and Simultaneous Estimation of Diclofenac Sodium and Nicotinamide
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Publication Date
Fri Dec 01 2023
Journal Name
Case Studies In Chemical And Environmental Engineering
Removal of copper from a simulated wastewater by electromembrane extraction technique using a novel electrolytic cell provided with a flat polypropylene membrane infused with 1-octanol and DEHP as a carrier
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Publication Date
Wed Sep 01 2021
Journal Name
Https://www.researchgate.net/journal/university-of-baghdad-engineering-journal-1726-4073
Evaluation of Drinking Water Quality in Al Wahda Treatment Plant in Baghdad City- Iraq
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This study aims to evaluate drinking water quality at the Al Wahda plant (WTP) in Baghdad city. A conventional water treatment plant with an average flow rate of 72.82 MLD. Water samples were taken from the influent and effluent of the treatment plant and analyzed for some physicochemical and biological parameters during the period from June to November 2020. The results of the evaluation indicate that treated water has almost the same characteristics as raw water; in other terms, the plant units do not remove pollutants as efficiently as intended. Based on this, the station appears to be nothing more than a series of water passage units. However, apart from Total dissolved solids, the mean values of all parameters in the study were

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Publication Date
Tue Aug 07 2018
Journal Name
Indian Journal Of Natural Sciences
Evaluation of Drinking Water Quality in Al Wathba Treatment Plant in Baghdad City-Iraq
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Publication Date
Wed Sep 01 2021
Journal Name
Journal Of Engineering
Evaluation of Drinking Water Quality in Al Wahda Treatment Plant in Baghdad City- Iraq
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This study aims to evaluate drinking water quality at the Al Wahda plant (WTP) in Baghdad city. A conventional water treatment plant with an average flow rate of 72.82 MLD. Water samples were taken from the influent and effluent of the treatment plant and analyzed for some physicochemical and biological parameters during the period from June to November 2020. The results of the evaluation indicate that treated water has almost the same characteristics as raw water; in other terms, the plant units do not remove pollutants as efficiently as intended. Based on this, the station appears to be nothing more than a series of water passage units. However, apart from Total dissolved solids, the mean values of all parameters in th

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Publication Date
Wed Dec 01 2021
Journal Name
Journal Of Physics: Conference Series
Evaluation the Safety and Security Procedures used In X-ray Clinics in Al-Harthiya-Baghdad
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Abstract<p>Radiation is a form of energy, its emitted either in the form of particles such as α-particles and β-particles (beta particles including the electron and the positron) or waves such as sunlight, X-rays and γ-rays. Radiation found everywhere around us and it comes from many different sources naturally or man-made sources. In this study a questionnaire was distributed to people working in the field of X-rays that used for a medical imaging (X-ray and CT-scan) to evaluate the extent of awareness and knowledge in estimate the damage of ionizing radiation as a result of wrong use. The questionnaire was distributed to medical clinics in Al-Harithiya in Baghdad, which it’s considered as</p> ... Show More
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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Engineering
Prediction of Raw Water Turbidity at the Intakes of the Water Treatment Plants along Tigris River in Baghdad, Iraq using Frequency Analysis
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Different frequency distributions models were fitted to the monthly data of raw water Turbidity at water treatment plants (WTPs) along Tigris River in Baghdad. Eight water treatment plants in Baghdad were selected, with raw water turbidity data for the period (2008-2014). The frequency distribution models used in this study are the Normal, Log-normal, Weibull, Exponential and two parameters Gamma type. The Kolmogorov-Smirnov test was used to evaluate the goodness of fit. The data for years (2008-2011) were used for building the models. The best fitted distributions were Log-Normal (LN) for Al-Karkh, Al-Wathbah, Al-Qadisiya, Al- Dawrah and, Al-Rashid WTPs. Gamma distribution fitted well for East Tigris and Al-Karamah WTPs. As for Al-

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Engineering
Prediction of Raw Water Turbidity at the Intakes of the Water Treatment Plants along Tigris River in Baghdad, Iraq using Frequency Analysis
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Different frequency distributions models were fitted to the monthly data of raw water Turbidity at water treatment plants (WTPs) along Tigris River in Baghdad. Eight water treatment plants in Baghdad were selected, with raw water turbidity data for the period (2008-2014). The frequency distribution models used in this study are the Normal, Log-normal, Weibull, Exponential and two parameters Gamma type. The Kolmogorov-Smirnov test was used to evaluate the goodness of fit.  The data for years (2008-2011) were used for building the models. The best fitted distributions were Log-Normal (LN) for Al-Karkh, Al-Wathbah, Al-Qadisiya, Al-Dawrah and, Al-Rashid WTPs. Gamma distribution fitted well for East Tigris and Al-Karamah

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Publication Date
Sun Jan 02 2022
Journal Name
Journal Of Medicinal And Chemical Sciences
Microwave synthesis schiff Base from Drug and 1,10-phenanthroline/8_Hydroxy quinoline as a Co- ligand with complexes:cytotoxic, Antimicrobial, and DNA Interaction Efficacy
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