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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
Tue Oct 01 2024
Journal Name
Dental Hypotheses
Evaluation of Impact, Tensile, and Flexural Strength of Natural Wool Fiber Reinforced Polymethyl Methacrylate Denture Base Material: An In Vitro Study
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Introduction: This study was carried out to assess the effect of natural wool fiber addition on the impact, tensile, and flexural strengths of the heat-cured acrylic denture base material. Methods: Short wool fibers with and without chemical surface treatment were added to polymethyl methacrylate (PMMA) at a percentage of 0.25% by weight. A total of 90 acrylic specimens were prepared and divided into three groups according to the tests performed. Impact strength, tensile strength, and flexural strength tests were evaluated. The statistical analysis of the results data was performed using the one-way analysis of variance (ANOVA) test and Tukey’s post hoc test

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Methionine as a Spacer between Poly Acrylic acid and Ampicillin
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In this work a novel drug delivery system through modification of poly acrylic acid with Methionine as a spacer between the poly acrylic acid which was converted to its acyl chloride and reacted with Methionine as spacer unit which has been reacted with Ampicillin drug. In vitro drug release study had been conducted successfully in basic medium in pH 7.4 and acidic medium in pH 1.1 at 37?. Due to many problems associated with drug release and, this modification could decrease the side effect of drug. The prepared prodrug polymer was characterized by spectra method [FTIR and 1H?NMR]. Physical properties and intrinsic viscosity of drug polymer were determined. The good results were obtained in the presence of spacer unit with compar

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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)
Uric Acid as a Natural Scavenger of Peroxynitrite in a Sample of Iraqi Patients with Rheumatoid Arthritis
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Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with decreased antioxidant state .This study aim to investigate the status of oxidant/antioxidant in a sample of  Iraqi patients with RA and the role of peroxynitrite and its natural scavenger uric acid in them .This case-controlled study was conducted at Baghdad teaching hospital /Baghdad from December 2010-May 2011 . Twenty-five patients with mean age 39 years and 25 apparently healthy subject as controls with mean age 29 years were included in the study .Investigations include estimation of serum levels of nitric oxide (NO)  ,peroxynitrite (PN) , malondialdehyde (MDA)  , and uric acid (UA) .Serum PN levels were significantly elevated in RA patients a

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Publication Date
Mon Aug 08 2022
Journal Name
Egyptian Journal Of Chemistry
Synthesis, spectroscopic and liquid crystalline studies of dithiocarbamat derivatives of pyrazole type ligands and their metal complexes
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Publication Date
Thu May 23 2013
Journal Name
Journal Of The College Of Basic Education
Synthesis and Characterization of Benzoic Acid 2-Salicylidene Complexes with Selected Metal Ions
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Salicylaldehyde was reacting with 2-amino benzoic acid to produce the Schiff base ligand benzoic acid 2-salicylidene (L). The prepared ligand was identified by Microelemental Analysis, FT.IR and UV-Vis spectroscopic techniques. A new complexes of Co(II),Ni(II),Cu(II) and Zn(II) with Schiff base was prepared in aqueous ethanol with a (1:1) M:L. The prepared complexes were characterized using flame atomic absorption, (C.H.N) Analysis, FT.IR and UV-Vis spectroscopic methods as well as magnetic susceptibility and conductivity measurements. Biological activity of the ligand and complexes against three selected types of bacteria were also examined. Some of the complexes exhibit good bacterial activities. From the obtained data the tetrahedral str

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Publication Date
Fri Jun 09 2017
Journal Name
Iraqi National Journal Of Chemistry
Synthesis and Characterization of some New Oxazepine Compounds Derived from D-Erythroascorbic Acid
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This search include the synthesis of some new 1,3-oxazepine derivatives have been prepared, starting from reaction of L-ascorbic acid with dry acetone in presence of dry hydrogen chloride afforded the acetal (I). Treatment of the latter with p-nitrobenzoyl chloride in pyridine yielded the ester (II) which was dissolved in (65%) acetic acid in absolute ethanol yielded the glycol (III). The reaction of the glycol (III) with sodium periodate in distilled water at room temperature produced the aldehyde (IV). The compound (V) [4-(1,3-dioxoisoindolin-2-yl)benzoic acid] was synthesized by reaction p-aminobenzoic acid and phthalic anhydride in presence of (gla. CH3COOH). Reaction of compound (V) with thionyl chloride produced [4-(1,3-dioxoisoindoli

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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Ocular Pharmacology And Therapeutics
Formulation and<i>In Vitro</i>Evaluation of Cyclosporine-A Inserts Prepared Using Hydroxypropyl Methylcellulose for Treating Dry Eye Disease
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Publication Date
Fri Jan 01 2021
Journal Name
Aip Conference Proceedings
Highly-charged EDTA-2Na salt as a novel draw solution in pressure-retarded Osmosis process
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Publication Date
Fri Sep 30 2016
Journal Name
Iraqi Journal Of Science
Anti-Mullerian Hormone and Follicle Stimulating Hormone as Markers of Ovarian Agingin a Sample of Iraqi Women
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One-hundred and twenty Iraqi women (60 single women and 60 married women) with age ranges from (17-49) years have been involved in this study to estimate the levels of anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) as markers of ovarian aging. The descriptive data [age, body mass index (BMI), age at menarche, duration of menarche] have been recorded. Blood samples were collected from the studied women to determine the levels of AMH and FSH. The results revealed non-significant (p>0.05) differences in levels of AMH and FSH between single women and married women. A significant negative correlation was observed between AMH levels and age in single women (r=-0.519, p<0.05) and married women (r=-0.433, p<0.05). A no

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Publication Date
Sun Mar 06 2011
Journal Name
Baghdad Science Journal
The Calculation of the partical distribution function g(r12,r1) for Carbon Ion cases (C+2,C+3,C+4) in the position space
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The aim of this work is study the partical distribution function g(r12,r1) for Carbon ion cases (C+2,C+3,C+4) in the position space using Hartree-Fock's Wave function, and the partitioning technique for each shell which is represented by Carbon Ions [C+2 (1s22s2)], [C+3 (1s22s)] and [C+4 (1s2)]. A comparision has been made among the three Carbon ions for each shell. A computer programs (MATHCAD ver. 2001i) has been used texcute the results.

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