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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 Dec 09 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study The Anti-Asthmatic Activity of Guggulsterone In Ovalbumin-Induced Asthma In Rat
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Asthma is a chronic in?ammatory respiratory disease associated with the changes of asthmatic airway structural that result from interact remodeling and in?ammatory processes lead to obstruction of airway. Guggulsterone (GS) is a bioactive compound and plant steroid present in  guggul gum of Commiphora wightii, which has anti-inflammatory and antioxidant activities. This study designed to investigate of anti-inflammatory activity of gugglsterone in improvement of asthma. Forty eight healthy albino male rats divided to six groups, Group I: Control group (distal water), Group II: Positive control group (distal water) with sensitization, Group III: Guggulsterone (25 mg/kg/day) with sens

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Publication Date
Mon Mar 26 2012
Journal Name
Journal Of Kufa For Chemical Sciences
Synthesis and Characterization of some lanthanide Metal ions Complexes of Schiff Bases derived From p-fluoro benzoic acid and thiosemicarbazide
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Reaction of  p-fluoro benzoic acid with the thiosemicarbazide and salcialdehyde gave the new bidentate ligand .The prepared ligand Identified by FT-I.R and U.V-Visible spectcopic technique .Treatment of the prepared   ligand   with following metal ions  M=Tb(III),Eu(III),Nd(III) and La(III) ,in ethanol with a (1:1) M:L ratio and at pH=7 yielded series of neutral complexes as the general formula  [M LCl (H O ]. The prepared complexes were characterized using (FT-IR, UV-Vis) spectra , melting point, molar conductivity measurements . chloride ion content were also evolution by (mhor method) . The proposed structure of the complexes using program , chem office 3D(2004) .

Publication Date
Fri May 18 2018
Journal Name
Thesis
The Arabian killifish (Aphanius dispar) as a novel model for mycophysiological studies.
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Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, rev

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Publication Date
Sat Aug 03 2013
Journal Name
European Journal Of Scientific Research
Serum Levels of Anti Intrinsic Factor Antibodies and α1- Antitrypsin in Alcohol-Dependent Males
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Excess alcohol consumption is associated with numerous metabolic changes and homeostasis disturbances of many macro- and micro-elements in the body. It has been associated with multiple pathologies at all levels. In the digestive apparatus, alcohol has generally been related to its toxic effects upon the liver. Alpha-1 antitrypsin (α-1 AT or AAT) plays an important role in controlling inflammation, coagulation and repair mechanisms in the body and most α-1 AT in the body is produced by the liver; from the other hand, Intrinsic factor (IF), which is a glycoprotein produced by the parietal cells of the stomach is necessary for the absorption of vitamin B12 in the small intestine. This study was designed to assess serum levels of α-1 AT and

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Publication Date
Wed May 01 2013
Journal Name
Iraqi Journal Of Embryos And Infertility Research
Assessment and correlation of Anti-sperm antibod-ies to sperm parameters in normozoospermic men
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The immune infertility caused by anti-sperm antibodies (ASAs) represented about 10–20% of infertility among the couples. The ASAs interfere with sperm parameters such as sperm motility and sperm ability to penetrate cervical mucus, sperm-oocyte binding, and fertilization and embryo development. Objectives: The present study designed to assess semen analysis, presence of ASAs and DNA fragmentation index as well as correlation within these parameters in normzoospermic Iraqi subjects Patients, Materials, and Methods: A total number of Iraqi subjects (116) with range of age (20-51) years and their mean duration of infertility (4.70 ± 2.77). Seminal fluid for macroscopic and microscopic assessments done according to WHO 2010 criteria. The

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The Semilogy of the Narrative Structure in "Nisa'a Al Altabat" Novel: The Semilogy of the Narrative Structure in "Nisa'a Al Altabat" Novel
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Abstruct
This recearch is about studying the novel (doorstep’s women) by the Iraqi
narrator Hadia Hussian, and I choose Semiolog as a Curriculum for this
critical approach, because I think that this Semiotic curriculum has the ability
to read the Subjects and the narrative constructions. Which form the structure
of the novel starting from the little to the characters.
The focus is on many narrative constructions in the novel we have
studied the semiology of the tittle, the semiology of the cover, of the color, the
names of the characters and the semiology of the female characters.
First the focus of the novel is on the women’s characters because most
of it’s characters are women. Secondly because these

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Publication Date
Thu Feb 09 2023
Journal Name
Journal Of Educational And Psychological Researches
An Evaluation Study of the Classroom Activities within the Developed English Course (Flying High) for the High School First- Grade Students in View of Creative Thinking Skills
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The study aims to examine the classroom activities of the developed English course (Flying High) for the high school first-grade students, identify creative thinking skills appropriate for this grade, and show the extent the classroom activities involve these skills from the female- teachers ‘point of view. The study adopted the descriptive survey method. The study community consists of all (50) English female-teachers who teach high school first grade in Arar city during the academic year (1440 -1441 A.H, the first semester). The study was applied to all respondents. The researcher used a questionnaire as a study tool. The study revealed that the female-teachers reported their disagreement and refusal of the classroom activities in th

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Publication Date
Sat Nov 01 2014
Journal Name
Pigmentary Disorders
Vitiligo: Skin Malignancies and Tumor Suppressive Marker P53
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KE Sharquie, AA Noaimi, AR Bandar, SY Mohsin, Pigmentary Disorders, 2014 - Cited by 5

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Publication Date
Thu Nov 20 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Gingival and alveolar ridge tumor-like overgrowth lesions
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Background: Tumor-like overgrowth lesions of the oral mucosa are pathological growths that project above the normal contour of the oral surface. A practical classification can be made according to the site of origin, the etiology and the histological appearance. The aim of this article is to evaluate and analyze patients with gingival and alveolar ridge tumor-like overgrowth lesions in terms of surgical treatment, diagnosis and outcome. Materials and Methods: Patients complaining of these lesions were treated by surgical excision under local or general anesthesia; the excised lesions were submitted for histopathological examination, during the follow up period the patients were examined for complications and recurrence. Results: Pyogenic gr

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Publication Date
Sun Sep 01 2013
Journal Name
Journal Of Baghdad College Of Dentistry
Gingival and Alveolar Ridge Tumor - Like Overgrowth Lesions
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Background: Tumor-like overgrowth lesions of the oral mucosa are pathological growths that project above the normal contour of the oral surface. A practical classification can be made according to the site of origin, the etiology and the histological appearance. The aim of this article is to evaluate and analyze patients with gingival and alveolar ridge tumor-like overgrowth lesions in terms of surgical treatment, diagnosis and outcome. Materials and Methods: Patients complaining of these lesions were treated by surgical excision under local or general anesthesia; the excised lesions were submitted for histopathological examination, during the follow up period the patients were examined for complications and recurrence. Results: Pyogenic gr

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