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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 Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In vitro MIC of Itraconazole Against Different Isolates of Candida albicans
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In vitro antifungal susceptibility test of itraconazole was carried out against 38 isolates from nails, skin, oral cavity, vagina and wounds, This study was done in Ramadi Teaching Hospital in period from January to August 2010. According to the National Committee for Clinical Laboratory Standard (NCCLS ) M 27- A by using the broth dilution method. Inoculum size was 1-5X103 CFU/ ml, while final concentrations of itraconazole ranged from 0.025 – 6.4 μg / ml by using RPMI – 1640 broth media and the fungus was incubated at 35 oC.  No resistant stain was recorded. MIC ranged from 0.05 – 6.4 μg / ml and the Mean ± SEM was 0.89 ± 0.28. MIC for nail isolates was 0.05 –

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Publication Date
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Pancreatic Stone Protein/ regenerating Protein (PSP/reg) as a Biochemical Marker for prediction of Microvascular Complications of Type 2 Diabetes Mellitus
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Background: Type 2 diabetes mellitus (T2DM) characterized by insulin resistance (IR) and progressive decline in functional beta (β) cell mass partially due to increased β cell apoptosis rate. Pancreatic stone protein /regenerating protein (PSP/reg) is produced mainly by the pancreas and elevated drastically during pancreatic disorder. Beta cells are experiencing apoptosis that stimulate the expression of PSP/reg gene in surviving neighboring cells, and that PSP/reg protein is subsequently secreted from these cells which could play a role in their regeneration.

Objectives: To analyze serum levels of PSP/reg protein in T2DM patients and evaluate its correlation with the microvasc

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Publication Date
Wed Nov 02 2022
Journal Name
Res Militaris
Cultural Activities The Iraqi Ministry of Culture, Tourism and Antiquilies
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It’s an attempt to identify the cultural activities of the Ministry of Culture, Tourism and Antiquities, which are provided by the Ministry of Culture, Tourism and Antiquities and the departments affiliated with the Ministry of Culture only, not tourism and antiquities. The most important results areIs that the Ministry of Culture, Tourism and Antiquities has many cultural activities such as (festivals, exhibitions, conferences, fashion shows, concerts, musical evenings, theatrical and cinematic performances) in addition to literary series and cultural magazines, which are directed to the public in general, whether it is elite or not, and this shows the extent The importance of cultural activities published by the Ministry of Culture, Tou

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Publication Date
Mon Jul 03 2023
Journal Name
Journal Of Polymer & Composites
Metal Complexes of Cephalexin and Their Biological Activities: A Review
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Cephalexin and its derivatives are commonly utilized in the pharmaceutical and medicinal industry due to their biological and pharmaceutical activities, including anti-microbial, anti-cancer, anti-bacterial, and herbicidal activities as well as possessing high palatability and being useful for skin and joint infections. Interestingly, some organic drugs, including cephalexin, which exhibit toxicological and pharmacological properties, can be administered in forms of metal complexes. Many researchers have synthesized organic ligands derived from cephalexin in forms of Schiff bases and azo compounds which exhibited higher biological and medicinal properties when compared to cephalexin alone. One of the important features that make Schiff base

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Publication Date
Sun Jan 01 2023
Journal Name
Dental Hypotheses
Assessment of Elongation Percentage, Tensile, and Tear Strength of Filler Particles: An In Vitro Study
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Publication Date
Fri Feb 08 2019
Journal Name
Iraqi Journal Of Laser
Photodynamic Therapy for Leiomyosarcoma: In vitro study
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Leiomyosarcoma (smooth muscle tumor) is a rare type of a malignant neoplasm of smooth
muscle. It is a resistant cancer, generally not very responsive to chemotherapy, radiationand surgery.The
aim of this study was to evaluate photodynamic therapy (PDT) as a possible basis for treatment using
(650 nm)diode laser with methyleneblue (MB) as a photosensitizer on leiomyosarcoma (LMS)cell line
(L20B) in vitro. The cytotoxic effects of 650nm diode laser 0.052 W/cm2 (power density) at different
exposure time (10, 20, and 30 min) with methylene blue at different concentrations (0.01% ,0.1 % ,1%)
was investigated on LMS cell line (L20 B). The cytotoxic effect of laser was increased with increasing
irradiation time for a certai

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Publication Date
Fri Jan 01 2016
Journal Name
World Journal Of Experimental Biosciences
Detection of anti-Helicobacter pylori antibodies in sera of women with recurrent spontaneous abortion
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To determine the relationship between Helicobacter pylori infection and reproduction disorder (recurrent spontaneous abortion), twenty women patients who undergo spontaneous abortion during first trimester of pregnancy (20-38) years and have been investigated from 2015/12/1 -2016/3/1 and compared to fifteen healthy individuals. All subjects were carried out to measure anti-H. pylori IgA and anti- H. pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA). There was significant elevation (p≤ 0.05) in concentration of anti- H. pylori IgG Abs (6.30± 0.99) compared to control group (4.48± 0.61) and IgA Abs (5.42 ± 0.90 U /ml) as compared to control group (3.92 ± 0.41 U/ml). The percentage of H. pylori IgG and IgA was 20% and 25

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Dose-dependent Anti-inflammatory Effect of Silymarin in Experimental Animal Model of Acute Inflammation
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Silymarin, a flavolignans from seeds of ‘milk thistle’ “Silybum marianum” has been widely used from ancient times because of its excellent hepatoprotective action. It has been used clinically to treat liver disorders including acute and chronic viral hepatitis, toxin/drug-induced hepatitis and cirrhosis and alcoholic liver disease. The efficacy and dose-response effect of silymarin (125, 250 and 500 mg/kg) were assessed using egg albumin-induced paw edema in rats as a model of acute inflammation. In this model, 56 rats were used and allocated into 7 subgroups each containing 8 rats. All treatments were given intraperitonealy 30 minutes before induction of inflammation by egg albumin and then the increase

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Publication Date
Mon Feb 02 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An Extrafollicular Cystic Adenomatoid Odontogenic Tumor of the Mandible Associated with Clear Cell Calcifying Epithelial Odontogenic Tumor: A Rare Case Report
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Background: The adenomatoid odontogenic tumor is a relatively rare benign epithelial odontogenic tumor. It contains both epithelial and mesenchymal components. Few cases presented as an extrafollicular lesion or involve the mandible or associated with other odontogenic lesions. This paper represents a rare case of an extrafollicular AOT. Case presentation: A 24-year-old female had a painless swelling on the right side of the lower jaw since one-month duration. Intraorally there was a well defined fluctuant-blue swelling in the right alveolar premolar region measuring 1×2 cm obliterating the right lower buccal vestibule. Grade II mobility in the vital 44 and 45 teeth were observed. Panoramic radiographs showed a well-defined pear shaped

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Publication Date
Mon Oct 16 2023
Journal Name
Indonesian Journal Of Chemistry
Synthesis of Zn(II) and Co(II) Complexes with a Schiff Base Derived from Malonic Acid Dihydrazide for Photo-Stabilizers of Polystyrene
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In this study, novel Schiff base complexes with Zn(II) and Co(II) ions were successfully synthesized. The malonic acid dihydrazide was converted into the Schiff base ligand by combining it with 1-hydroxy-2-naphthaldehyde, and the last step required reacting it with the appropriate metal(II) chloride to produce pure target complexes. The generated complexes were thoroughly characterized using FTIR, 1H-NMR, 13C-NMR, GC-mass, and UV-Vis spectroscopies. In order to photo-stabilize polystyrene (PS) and reduce the photodegradation of its polymeric chains, these chemicals have been used in this work. The efficiency of the generated complexes as photo-stabilizers was evaluated using a variety of techniques, including FTIR, weight loss, visc

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