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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
Mon Dec 16 2024
Journal Name
Polimery
Synthesis and photochemical stability of polymeric derivatives formed by the reaction of acrylamide and succinic anhydride copolymer with dyes
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A new derivative of PAM, acrylamide was copolymerized with succinic anhydride, and the reaction product reacted with three dyes, anthocyanin, bromophenol, and thymol. The prepared polymers were characterized by X-ray diffraction, FT-IR and UV-visible spectroscopy, proton nuclear magnetic resonance spectrometry, and thermal analysis. FT-IR spectroscopy showed the disappearance of two bands near 3450 and 3380 cm-1 for the stretching vibrations of the primary amine which indicates for the formation of amides. The UV-photolysis of aqueous solutions of different concentrations of the polymers was studied. Polyacrylamide-g-succinic anhydride showed an increase in polymerization under light. An increase of ~ 50% was observed for a 200 mg/L

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Publication Date
Fri Feb 01 2019
Journal Name
Meta Gene
Cytokine gene variations and their impact on serum levels of IFN-γ, IL-2, IL-4, IL-10 and IL-12 among Iraqi Arabs
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Publication Date
Sun Dec 02 2012
Journal Name
Baghdad Science Journal
Synthesis, spectroscopic study of Pt (IV), Au (III), Rh(III),Co(II) and V (IV) complexes with sodium[5-(p-nitro phenyl) -/4- phenyl-1,2,4-triazole-3-dithiocarbamato hydrazide] and cytotoxicity assay on rhabdomyosarcoma cell line of heavy metals
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All the prepared metal complexes of Pt (IV), Au(III), Rh (III), Co (II) and V(IV) with new ligand sodium [5-(p-nitro phenyl)-/4-phenyl-1,2,4-triazole-3-dithiocarbamato hydrazide] (TRZ.DTC) have been synthesized and characterized in solid state by using flame atomic absorption, elemental analysis C.H.N.S, FT-IR ,UV-Vis Spectroscopy, conductivity and magnetic susceptibility measurements. The nature of the complexes formed in ethanolic solution has been studied following the molar ratio method also was studied stability constant and found to be stable in molar ratio1:1 of VL (IV) and CoL(II) while Pt(IV), Au(III) and Rh(III) complexes stable in molar ratio 1:2 as well as the molar absorptivity for these complexes were calculated. From the prev

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
A Feminist Stylistic Analysis of Anti-feminist Poetry in English and Arabic
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Language plays a major role in all aspects of life. Communication is regarded as the most important of these aspects, as language is used on a daily basis by humanity either in written or spoken forms. Language is also regarded as the main factor of exchanging peoples’ cultures and traditions and in handing down these attributes from generation to generation. Thus, language is a fundamental element in identifying peoples’ ideologies and traditions in the past and the present. Despite these facts, the feminist linguists have objections to some of the language structures, demonstrating that language is gender biased to men. That is, language promotes patriarchal values. This pushed towards developing extensive studies to substantiate s

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Publication Date
Wed Dec 15 2021
Journal Name
Al-adab Journal
A Feminist Rhetorical Analysis of Anti-feminist Poetry in English and Arabic
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Publication Date
Sun Feb 03 2019
Journal Name
Iraqi Journal Of Physics
Assessment of radiological risk in the area around surface disposal at Al -Tuwaitha site
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The gamma dose rates and specific activity of 137Cs, 60Co and 40K in
samples of soil taken from places near the landfill radiation at Al-
Tuwaitha site were measured using a portable NaI(Tl) detector. The
results of gamma dose rates in samples were ranged from 52.6
nGy.h-1 to 131nGy.h-1. Then the specific activity of 137Cs, 60Co and
40K in soil were determined using high pure germanium (HPGe)
detector. The specific activities were varied from 1.9 to 115500 Bq.
kg-1 for 137Cs, from 6.37 to 616.5 Bq. kg-1 for 60Co, and from 3 to
839.5 Bq. kg-1 for 40K. The corresponding health risk for the annual
effective dose equivalent varied from 1.85×10-14 to 15.7mSv/y. The
results were compared with various internationa

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Publication Date
Sat Feb 21 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An evaluation of three fissure sealants microleakage with presence or absence of bonding agent through time intervals (In vitro study)
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Background: Pit and fissure sealant have been considered an outstanding adjunct to oral health care in the decrease of occlusal caries onset and low progression. The aims of this in vitro study were to evaluate the marginal microleakage of three different types of fissure sealants (SDI, Tg and tetric N-flow) by time interval, one day and 45 days, in the presence or absence of bonding agent among maxillary and mandibular teeth. Materials and methods: Seventy two sound human maxillary and mandibular first premolar teeth were collected which were free from obvious carious lesions. The teeth were randomly divided into two main equal groups, group (1) and group (2), each group consists of (36) teeth involving equal numbers of maxillary and mandi

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Publication Date
Mon Jul 10 2023
Journal Name
Russian Journal Of Bioorganic Chemistry
Synthesis and Characterization of New 1,3,4-Oxadiazole Ring on Creatinine Derivatives Using Iodine and Study Their Anticancer Effect
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Publication Date
Sun Jan 01 2012
Journal Name
Kerbala Journal Of Pharmaceutical Sciences
Synthesis of new Schiff bases and nucleoside analogues derivatives derived from D-Glucose and their biological activity study
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Inthis study new derivatives of Schiff bases and nucleoside analogues have been synthesized from the starting material D-glucose after a series of reactions. Derivative 1 was prepared from D-glucose then react with P-bromoacetophenone gave derivative 2 was reacted with dimethyl sulfoxide and acetic anhydride for dehydration a molecule of water gave 3. The spiro ring was prepared at 3-position from the reaction of 3 derivative with 1-phenyl-2–thioureagave 4. The protection group at 1 position was removed by using acetic acid fllowed by periodate oxidation to obtain 6. Reaction of 6 with hydrazide derivative at once and dtriazole derivative at another gave 8 and 9 respectively. Compound 6 was reduced to gave derivative 7. The 1-hydroxylgrou

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Publication Date
Thu Jan 01 2015
Journal Name
Journal Of Chemical And Pharmaceutical Research
Studies on the interaction and effect of Mn(II), Fe(II), Co(II), Ni(II),Cu(II), Zn(II) and Cd(II) mixed- ligand complexes of cephalexin mono hydrate and furan-2-carboxylic acid to different DNA sources
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To evaluate the Interaction of Mn(II), Fe(II), Co(II), Ni(II),Cu(II), Zn(II) And Cd(II) Mixed- Ligand Complexes of cephalexin mono hydrate (antibiotics) And Furan-2-Carboxylic Acid To The Different DNA Sources. All the metal complexes were observed to cleave the DNA. A difference in the bands of complexes .The cleavage efficiency of the complexes compared with that of the control is due to their efficient DNA-binding ability and the other factors like solubility and bond length between the metal and ligand may also increase the DNA-binding ability. The ligands (Cephalexin mono hydrate (antibiotics) and Furan-2- Carboxylic acid and there newly synthesized metal complexes shows good antimicrobial activities and Binding DNA , thus, can be used

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