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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 Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Characterization of Isradipine as Oral Nanoemulsion
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        Isradipine related to dihydropyridine (DHP) class of calcium channel blockers (CCBs). It is  used to treat hypertension, angina pectoris, as well as Parkinson disease. It goes under the BCS class II drug (low solubility-high permeability). The drug will experience extensive first-pass metabolism in liver, thus, oral bio-availability will be approximately15 to 24 %. 

       The aim of the study is preparing stable oral oil in water (o/w) nanoemulsion of isradipine to promote the colloidial dispersion of isradipine in the nano range, so that it may be absorded by intestinal lymphatic transport in order to avoid hepatic first-pass metabolism (israpidi

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Publication Date
Sun Jun 21 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Investigation of Lacidipine as a Nanoemulsions
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Many pharmaceutical molecules have solubility problems that until yet consist a hurdle that restricts their use in the pharmaceutical preparations. Lacidipine (LCDP) is a calcium-channel blocker with low aqueous solubility and bioavailability.

        Lipid dosage forms are attractive delivery systems for such hydrophobic drug molecules. Nanoemulsion (NE)  is one of the popular methods that has been used to solve the solubility problems of many drugs. LCDP was formulated as a NE utilizing triacetin as an oil phase, tween 80 and tween 60 as a surfactant and ethanol as a co-surfactant. Nine formulas were prepared, and different tests performed to ensure the stability of the NEs, such as thermodyna

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Publication Date
Mon Mar 13 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Comparative Study of The Amount of Apically Extrusion Of Debris During Root Canal Preparation Using Wave Oneâ„¢, Trushape 3Dâ„¢, Hyflexâ„¢ CM and One Shapeâ„¢ Instrumentation Systems (An In Vitro Study)
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Background: Many types of instruments and techniques are used in the instrumentation of the root canal system. These instruments and techniques may extrude debris beyond the apical foramen and may cause post-instrumentation complications. The aim of this study was to evaluate the amount of apically extruded debris resulted by using 4 types of nickel-titanium instruments (WaveOne, TRUShape 3D conforming files, Hyflex CM, and One Shape files) during endodontic instrumentation. Materials and methods: Forty freshly extracted human mandibular second premolar with straight canals and a single apex were collected for this study. All teeth were cut to similar lengths. Pre-weighted glass vials were used as collecting containers. Samples were randoml

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Publication Date
Fri Feb 20 2026
Journal Name
Sciences Journal Of Physical Education
Leadership patterns for university student activities managers according to the Blake and Moton model (The managerial Grid)
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The researcher is one of the workers in university sports student activities, as he noticed that there is a diversity in the use of leadership patterns among managers of student activities in Iraqi universities between one director and another, which leads to the impact of these leadership styles on performance, positive or negative, in the level of human relations and the achievement of results. The researcher adopted the descriptive method in the survey method with relational relationships. The research sample consisted of (184) sports coaches who represent (27) universities and governmental and private colleges. To achieve the research objectives, the researcher used the Statistical Package for Social Sciences (Spss). To extract.statisti

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Publication Date
Fri Dec 01 2023
Journal Name
International Society For The Study Of Vernacular Settlements
Evaluation of Sustainability Using LEED Rating Scales: The Bismayah New City in Baghdad, Iraq
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Publication Date
Thu Feb 01 2024
Journal Name
Journal Of Engineering
The Economic Evaluation of Various Production Scenarios for Zubair Reservoir in the Kifl Field
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This work evaluates the economic feasibility of various production scenarios for the Zubair reservoir in the Kifl oil field using cash flow and net present value (NPV) calculations. The Kifl field is an exploratory field that has not yet been developed or assessed economically. The first well was drilled in 1960, and three other wells were later drilled to assess the oil accumulation, so in this research, Different production scenarios were evaluated economically. These scenarios were proposed based on the reservoir model of the Zubair formation in the field. The research methodology used QUE$TOR software to estimate capital expenditures (CapEx) and operating expenditures (OpEx) based on field-level data, production prof

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Publication Date
Sun Dec 04 2011
Journal Name
Baghdad Science Journal
Evaluation the levels of Plasma Interleukins (IL-8, IFN-?, IL-10) in Preeclamptic Pregnancies
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This study is to evaluate plasma levels of several cytokines in preeclamptic pregnancies compared to those of healthy pregnancies. Ninety pregnant women with preeclampsia (37 mild & 53 severe) and thirty healthy pregnant women were enrolled in the study. Blood samples were taken and plasma levels of IL-8, IL-10, and IFN-? were measured by enzyme-linked immunosorbent assay (ELISA). Preeclamptic women and their severe cases but not mild cases had significantly (P<0.05) increased levels of plasma IL-8, and IFN-? as compared with healthy pregnancies. By contrast, plasma levels of IL-10 was significantly (P<0.05) increased in healthy pregnant women as compared to all groups of preeclampsia. Preeclampsia is associated with an imbalance betwe

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Publication Date
Mon Dec 01 2014
Journal Name
Al Mustansiriyah Journal Of Pharmaceutical Sciences
Evaluation of the Predisposing Factors for Recurrent Respiratory Tract Infections in Iraqi Pediatric Patients.
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Recurrent respiratory tract infections are responsible for about 85% of all diseases in childhood, and are associated with significant morbidity and mortality. The aim of this study is to evaluate the main causes underlying recurrent respiratory tract infections in 176 pediatric patients aged 2 month to 4 year and weight from 4 to11 kg referred to the child center hospital and Al-sader hospital prospective study.All parents were given information sheet which then analyzed and the percentage of incidence of causes were recorded, we found that higher % related to many causes; mostly related to the parent like poor family education, mother carelessness, incomplete vaccination, other related to empirical diagnosis, and short course of t

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Publication Date
Fri Feb 01 2019
Journal Name
Iraqi Journal Of Information &amp; Communications Technology
Evaluation of DDoS attacks Detection in a New Intrusion Dataset Based on Classification Algorithms
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Intrusion detection system is an imperative role in increasing security and decreasing the harm of the computer security system and information system when using of network. It observes different events in a network or system to decide occurring an intrusion or not and it is used to make strategic decision, security purposes and analyzing directions. This paper describes host based intrusion detection system architecture for DDoS attack, which intelligently detects the intrusion periodically and dynamically by evaluating the intruder group respective to the present node with its neighbors. We analyze a dependable dataset named CICIDS 2017 that contains benign and DDoS attack network flows, which meets certifiable criteria and is ope

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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Evaluation the water quality of the potable water network in Al-Shuala/ Baghdad City
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In this research, the water quality of the potable water network in
Al-Shuala Baghdad city were evaluated and compare them with the
Iraqi standards (IQS) for drinking water and World Health
Organization standards (WHO), then water quality index (WQI) were
calculator: pH, heavy metals (lead, cadmium and iron), chlorides,
total hardness, turbidity, dissolved oxygen, total dissolved solid and
electrical conductivity. Water samples are collected weekly during
the period from February 2015 to April 2015 from ten sites. Results
show that the chlorides, total dissolved solid and electrical
conductivity less than acceptable limit of standards, but total
hardness and heavy metals in some samples higher than acceptabl

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