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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
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Six-coordinate oxime-imine cobalt(III) complexes with amino acid co-ligands; synthesis and characterisation
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In this publication, several six coordinate Co(III)-complexes are reported. The reaction of 2,3-butanedione monoxime with ethylenediamine or o-phenylenediamine in mole ratios of 2:1 gave the tetradentate imine-oxime ligands diaminoethane-N,N`-bis(2-butylidine-3-onedioxime) H2L1 and o-phenylenediamine-N,N`-bis(2-butylidine-3-onedioxime), respectively. The reaction of H2L1 and H2L2 with Co(NO3)2, and the amino acid co-ligands (glycine or serine) resulted in the formation of the required complexes. Upon complex formation, the ligands behave as a neutral tetradantate species, while the amino acid co-ligand acts as a monobasic species. The mode of bonding and overall geometry of the complexes were determined through physico-chemical and spectro

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Publication Date
Mon Mar 12 2018
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Effect of Crystallization Time and Acid Type on the Synthesis of Nano-Gamma Alumina Using Double Hydrothermal Method
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Double hydrothermal method was used to prepare nano gamma alumina   using aluminum nitrate nano hydrate and sodium aluminate as an aluminum source, CTAB (cetyltrimethylammonium bromide) as surfactant, and variable acids: weak acids like; citric, and acitic acids, and strong acids like; hydrochloric and nitric acids as a bridge between aluminum salts and surfactant. Different crystallization times  12, 24, 48, and 72 hrs were applied. All the batches were prepared at pH equals to 9. XRD diffraction technique was used to investigate the crystalline nano gamma alumina pure from surfactant. N2 adsorption-desorption (BET) was used to measure the surface area and pore volume of the prepared nano alumina, the average p

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Publication Date
Tue Aug 30 2022
Journal Name
Research Journal Of Pharmacy And Technology
Correlation of Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with serum GDF-15 in a group of hypertensive Iraqi patients
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The Growth Differentiation Factor -15 (GDF-15) is a member of the transforming growth factor β superfamily. İt represents an example of the stress response cytokines. It's mostly found in cardiac myocytes, adipocytes, macrophages, endothelial cells, and vascular endothelial cells, whether they're generated normally or not. GDF-15 levels have increased and are associated with cardiovascular risk. Aim of the study: To investigate the correlation between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) with the level of plasma GDF-15 in a group of hypertensive patients. Materials and methods: A case-control study involved 90 individuals, 60 hypertensive patients (36 on ACE inhibitors and 24 on ARBs)

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Publication Date
Sat Oct 01 2022
Journal Name
Al–bahith Al–a'alami
PHARAOH'S CHARACTER BETWEEN THE QUR'ANIC TEXT AND THE ARABIC NOVEL: (Naguib Mahfouz's Pharaonic Novels as a Model)
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The Character is one of the elements of Storytelling, as it is the center of the plot, making it the basis on which the talk is about. The talk is the portrayal of the character while they’re acting; the novelist presents the character by interacting with the events, and the extent of the negative and positive appearing impact on the character. It should be noted that everyone has two personalities or more, each one appearing in a different position or situation. For instance, a man can be a father, a lover, an employee, a son or anyone else .. in another position, he might be a master, and in another a looser begging for the mercy of his humiliator, and sometimes he can show weakness to the one he loves, or show strength to his enemie

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Publication Date
Thu May 04 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
In Vitro Propagation of Groundnut (Arachis hypogea L.)
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A protocol has been developed for micropropagation of Arachis hypogea L. under in
vitro conditions. Nodal explants gave rise to multiple shoots when cultured on MS medium
supplemented with different concentrations of BA (benzyladenine) with Kin (Kinetin) or GA3
(gibberellic acid). The highest response of shoot multiplication was obtained in MS
containing 1.5 mg.l¯¹ BA and 0.5 mg.L¯¹ Kin. The regenerated shootlets were rooted on MS
(Murashige and Skoog) basal medium with different concentrations of IBA (indolbutyric
acid) and IAA (indol acetic acid). The highest response of rooting was achieved with IBA at
0.05 + IAA at 0.05 mg.L¯¹. The maximum frequency of rooting and highest number of roots

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Publication Date
Sun May 14 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Antibacterial Activity of Calendula Officinalis Flowers In Vitro
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        Flower  samples of Calendula officinalis were collected from the gardens of the college of Pharmacy in Baghdad city  to examine their antibacterial activity .The effect of ethanol crude extract of petals and reproductive parts of flowers in different concentrations were obtained and bioassayed in vitro for its bioactivity to inhibit the growth of eight types of bacteria .The extracts of petals  part were clearly superior for all bacteria especially the bacteria Pseudomonas aeruginosa (inhibition zone was 25mm in the concentration 100mg/ml) from gram negative bacteria, and Staphylococcus aureus (inhibition zone was 14mm in the concentration 50mg/ml) from gram positive bacteria, whi

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Phytochemical Study of Cynara scolymus L. (Artichoke) (Asteraceae) Cultivated in Iraq, Detection and Identification of Phenolic Acid Compounds Cynarin and Chlorogenic Acid
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The leaves of globe artichoke, Cynara scolymus Family Asteraceae/ compositea have long – used in traditional medicine and now included in British and European Pharmacopeia, the British Harbal Pharmacopeia and complete German Commission E monographs.The plant originally comes from Mediterranean region and North Africa and cultivated around the world. The flowers are used worldwide for nutrition purposes and the leaves for medical purposes including hepatic affections. The plant wildly distributed in Iraq in the watery lines and boundary of the field.The plant contains many phytochemicals such as the bitter phenolic acids whose choleretic and hypocholestremic as these compounds are antioxidant. Other materials to h

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Publication Date
Fri Jan 26 2024
Journal Name
Iraqi Journal Of Science
Removal of Cu (ll) From Aqueous Solution Using Polyacrylic Acid Hydrogel Beads as Adsorbent
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In this article, the adsorption of Cu(ll) ion from aqueous solution into polyacrylic acid
(PAA) hydrogel bead has been investigated using a batch method of different
temperature (10-30 °C) and different contact time (1-48 hr) to reach the equilibrium of
adsorption. Initial concentration and adsorption capacity of the adsorbents is presented,
the time required to reach a maximum capacity of bead was about 24hr. The temperature
effect on adsorption was studied and the experimental data have been analyzed using the
Langmuir and freundlich isotherm models. The adEsorption capacity at equilibrium was
found to be 142.68 mg/g; more than 95% of studied cation was removed by the
adsorbent. The process is very efficient es

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Publication Date
Wed Feb 08 2023
Journal Name
Iraqi Journal Of Science
Heavy Metals Pollution Assessment of the Soil in the Northern Site of East Baghdad Oil Field, Iraq
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Twenty four soil samples were collected from different sites in north sector of East Baghdad oil field, Iraq , and analyzed to assess the impact of urbanization and industrialization essential pollution. The soil samples were analyzed for heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) by using inductively coupled plasma–mass spectrometry (ICP-MS). Mean concentration of heavy metals in soil samples follows this pattern: Zn > Ni > Cr > Cu >Pb > As> Cd> Hg. The results show significant variations (lower and higher) in the concentrations of heavy metals compared with local and world studies, this variation is attributed to the natural anthropogenic sources. The pollution of studied soil was assessed using many soil

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Publication Date
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Calcium Oxide Impregnated on Silica from Duck Egg Shells and Rice Husks as Heterogeneous Catalysts for Biodiesel Synthesis
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Biodiesel can be prepared from various types of vegetable oils or animal fats with the aid of a catalyst.
Calcium oxide (CaO) is one of the prospective heterogeneous catalysts for biodiesel synthesis. Modification
of CaO by impregnation on silica (SiO2) can improve the performance of CaO as catalyst. Egg shells and rice
husks as biomass waste can be used as raw materials for the preparation of the silica modified CaO catalyst.
The present study was directed to synthesize and characterize CaO impregnated SiO2 catalyst from biomass
waste and apply it as catalyst in biodiesel synthesis. The catalyst was synthesized by wet impregnation
method and characterized by x-ray diffraction, x-ray fluorescence, nitr

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