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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 Jun 01 2016
Journal Name
Journal Of Engineering
Management Model for Evaluation and Selection of Engineering Equipment Suppliers for Construction Projects in Iraq
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Engineering equipment is essential part in the construction project and usually manufactured with long lead times, large costs and special engineering requirements. Construction manager targets that equipment to be delivered in the site need date with the right quantity, appropriate cost and required quality, and this entails an efficient supplier can satisfy these targets. Selection of engineering equipment supplier is a crucial managerial process .it requires evaluation of multiple suppliers according to multiple criteria. This process is usually performed manually and based on just limited evaluation criteria, so better alternatives may be neglected. Three stages of survey comprised number of public a

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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
Tue Jun 17 2025
Journal Name
Research In Social Sciences
Using Chatbot and ChatGPT as Useful Tools in Scientific Academic Writing
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This review investigates the practice and influence of chatbots and ChatGPT as employable tools in writing for scientific academic purposes. A primary collection of 150 articles was gathered from academic databases, but it was systematically chosen and refined to include 30 studies that focused on the use of ChatGPT and chatbot technology in academic writing contexts. Chatbots and ChatGPT in writing enhancement, support for student learning at higher education institutions, scientific and medical writing, and the evolution of research and academic publishing are some of the topics covered in the reviewed literature. The review finds these tools helpful, with their greatest advantages being in areas such as structuring writings, gram

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Publication Date
Sun Dec 31 2023
Journal Name
International Journal For Humanities & Social Sciences (ijhs)
‘Ambivalence’ as a Concept in John Clare's Middle and Late Poetry
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        This paper signifies the contradictory point of view in John Clare’s poetry. Clare (1794-1864) is an English romantic poetry in the nineteenth century, who writes more than ten volumes about nature. So, this study highlights the concept of Psychoanalytic theory which is ‘ambivalence’ and how through this theory can interpret any literary text on the basis of utilizing psychoanalytic methods to literary texts in order to reveal the author's inner emotions such as motives, dreams, as well as wishes. Consequently, the concept of  ‘ambivalence’ has a lot in common with the human psyche and its struggles. Sometimes the reader finds the author/poet talking about something real or a notion with pleasant sentiments

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Publication Date
Sun Jun 30 2024
Journal Name
Romanian Medical Journal
Serum and urine apolipoprotien A1 (ApoA1) as biomarkers in bladder cancer
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Bladder cancer (BC) is the predominant malignant neoplasm in the urinary system and ranks as the tenth most prevalent malignant tumor worldwide. Compared with females, males displayed a four-fold more common incidence of bladder cancer. It mainly affects men. Bladder cancer is the fourth most prevalent neoplasm in males. The most important protein that makes up high density lipoprotein (HDL), ApoA-I apolipoprotein A1 is essential in regulating the right amount of cholesterol. Multiple inquiries have demonstrated that APOA1 plays a pivotal role in the progression, infiltration, and spread of tumors. Objectives. The objective of this study was to measure the level of urine to serum apolipoprotein A1 in patients suffering from bladder

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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
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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