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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 01 2023
Journal Name
Australian Dental Journal
Debonding of LDSVs utilising Er,Cr:YSGG laser irradiation with fractional technique: an in vitro study
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Publication Date
Tue May 01 2018
Journal Name
Photomedicine And Laser Surgery
In Vitro Influence of Low-Power Diode Laser Irradiation Time on Human Red Blood Cells
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Objective: The present study investigates whether the exposure to low-power diode laser induces denaturation in red blood cell (RBC) membrane protein composition, and determines the irradiation time for when denaturation of membrane protein process begins. Background: A low-energy laser has been used extensively in medical applications. Several studies indicated significant positive effects of laser therapy on biological systems. In contrast, other studies reported that laser induced unwanted changes in cell structure and biological systems. The present work studied the effect of irradiation time of low-power diode laser on the structure of membrane proteins of human RBCs. Materials and methods: The RBC suspension was divided into five equa

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Publication Date
Sun Feb 24 2019
Journal Name
Iraqi Journal Of Physics
Synthesis of polyynes by laser ablation of graphite in ethanol
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In this work  Polyynes was synthesized by pulse laser ablation of graphite target in ethanol solution. UV-Visible Spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR) and Transmission electron microscopy (TEM) were used to study the optical absorption, chemical bonding, particle size and the morphology.  UV absorption peaks coincide with the electronic transitions corresponding to linear hydrogen – capped polyyne (Cn+1H2), the absorption peaks intensity increased when the polyynes were produced at different laser energies and the formation rats of polyynes increased with the increasing of laser pulse number. The FTIR absorption peak at 2368.4 cm-1, 1640.0 cm-1 and 1276.

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Publication Date
Sun Mar 04 2018
Journal Name
Baghdad Science Journal
Synthesis and Characterization of a Molecularly Imprinted Polymer for Diclofenac Sodium Using (2-vinylpyridine and 2-hydroxyethyl metha acrylate) as the Complexing Monomer
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Four electrodes were synthesized based on molecularly imprinted polymers (MIPs). Two MIPs were prepared by using the diclofenac sodium (DFS) as the template, 2-hydroxy ethyl metha acrylate(2-HEMA) and 2-vinyl pyridine(2-VP) as monomers as well as divinyl benzene and benzoyl peroxide as cross linker and initiator respectively. The same composition used for prepared non-imprinted polymers (NIPs) but without the template (diclofenac sodium). To prepared the membranes electrodes used different plasticizers in PVC matrix such as: tris(2-ethyl hexyl) phosphate (TEHP), tri butyl phosphate (TBP), bis(2-ethyl hexyl) adipate (BEHA) and tritolyl phosphate (TTP). The characteristics studied the slop, detection limit, life time and linearity range of DF

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Publication Date
Fri Nov 25 2022
Journal Name
Baghdad Science Journal
Evaluation of Some Antioxidants and Oxidative Stress Tests in Iraqi Lung Cancer Patients
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Vitamin K-dependent protein (VKDP) contributes to the development of lung cancer. The purpose of this research was to better understanding of the role of blood matrix Gla protein (MGP), VKDPs, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Vitamin K (Vit K) in Iraqi patients with lung cancer before and after the first cycle of chemotherapy. Blood samples were collected from Al amal National Hospital for cancer treatment from October 2021 to May 2022, and a total of 80 samples were collected, divided into two groups (40 patient before taking a chemotherapy and 40 patients after taking chemotherapy), ranging in age from 20 to 45 years old. The results showed that although there were highly statistically significant differences in MD

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Evaluation the Levels of Serum Hormones (Progesterone, Estradiol, and hCG) in Preeclamptic IraqiPregnancies
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This study aimed to evaluate serum levels of steroid hormones and human chorionic gonadotropin (hCG) hormone in preeclamptic Iraqi pregnancies compared to those of healthy pregnancies.This study enrolled 120 pregnant women, divided into four groups:1. 30 healthy pregnant women.2. 37 pregnant women with mild preeclampsia3. 53 pregnant women with severe preeclampsia4. 90 pregnant women with preeclampsia Preeclamptic women and their severe cases but not mild cases had significantly (P<0.01) increased levels of serum hCG as compared with healthy pregnancies. By contrast, sera levels of estradiol were significantly (P<0.01) decreased in total preeclamptic groups and their severe cases but not in mild group as compared to healthy pregnant wome

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Publication Date
Sun Jun 02 2013
Journal Name
Baghdad Science Journal
Evaluation of ELectrolytes in Adult Patients with Acute Leukemia before and after Chemotherapy
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Abstract:Leukemia is a cancer of early blood forming cells. Most of them are cancers of white blood cells , however some leukemias start in other blood cell types.Electrolytes have modulatory effects on several biological mechanisms in the body namely as stabilizers,element of structures, essential element for hormonal function and also co-factors for a number of enzymes.In this study serum electrolytes levels were measured in patients with acute leukemia (AL) disorders before and after chemotherapy(anthracycline, doxorubicin, cytarabine ,prednisone, vincristine and doxorubicin) during one month and compared with that of control group. Blood samples were obtained from (43) patients (28 males and 15 females) aged (15-55)years;juset before an

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Evaluation of some biochemical and immunological parameters changes in Iraq male with toxoplasmosis
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A total of 33 Iraq male positive for Toxoplasmosis and Iraq male negative for Toxoplasmosis (controls) were studies to Evaluation of some biochemical and immunological parameters changes.The parameters included lipid profile such as (Cholesterol(C), Triglycerides(TG), High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL) and very Low-Density Lipoprotein (VLDL) and complement component C3 and C4. The results revealed significant decrease in the total cholesterol, Triglycerides, LDL and non-significant in vLDL (129.96±1.63, 130.69± 2.80, 87.19±1.97, 29.24± 0.83 mg/dl respectively) and non-significant increase in HDL(24.22 ±0.62) mg/dl compared with control group(152.07± 1.63, 156.48± 6.55, 99.26 ±1.39, 31.49± 1.30 and 21.31±

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Publication Date
Mon Jul 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Evaluation of some Biochemical and Hematological Parameters in Patients with Chronic Kidney Disease
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Background: Chronic kidney disease is a condition that results from an indefinite change in the structure and function of the kidneys. A slow, steady progression characterizes it and is irreversible.  Objectives: This study aims to evaluate the findings of certain biochemical and hematological tests in samples from Iraqi CKD patients.  Methods: This study included 90 subjects, where 70 patients with chronic kidney disease and 20 healthy individuals. Blood samples were collected from the patients during their visits to Ghazi Al-Hariri Surgical Specialties' Hospital- Medical City, Baghdad, Iraq. Age, sex and body mass index were assessed for each participant followed by renal function tests [serum blood urea, creatinine, uric acid a

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Publication Date
Tue Jun 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
Effect of phosphorous and amino acid on growth and yield of pea
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