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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.

Scopus Clarivate Crossref
View Publication
Publication Date
Sun Aug 15 2021
Journal Name
Annals Of R.s.c.b.
Versatile Applications of Complexes with Some Lanthanide Elements: A Review
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Cerium (III), Neodymium (III) and Samarium (III) Complexes existent a wide range of implementation that stretch from their play in the medicinal and pharmaceutical area because of their major significant pharmacological characteristic such as antifungal, anti-cancer, anti-bacterial ,anti-human immunodeficiency virus ,antineoplastic, anti-inflammation,inhibition corrosion,in some industrial (polymers, Azo dye).It is likely to open avenuesto research among various disciplines such as physics, electronics, chemistry and materials science by these complexes that contain exquisitely designed organic molecules.This paper reviews the definition, importance and various applications of Cerium (III), Neodymium (III) and Samarium (III) Complexes anddi

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Publication Date
Sat Dec 01 2018
Journal Name
Political Sciences Journal
Handicaps of reconstructing Iraqi strategic capabilities after 2003 (Analytical vision )
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Abstract: The issue of rebuilding the strategiccapacity of Iraq after the occupation and the US invasion in 2003 has been oneof the most contentious issues of debate and debate. It raises a number ofpolitical, social, economic, military and security problems. We say politicalprimarily because the climate and political conditions play a large and activerole along with other factors complementary to them. The important questionthat arises here is: How can the ruling political blocs move to the stage ofreconstruction without reservations? In order to answer this question, wedivided the study into three main axes. The first deals with the concept ofpower and its types. The second axis deals with the relationship betweenstrategic capa

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Crossref
Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Pharmacy And Biological Sciences
Genetic Polymorphism of Iraqi Leishmania tropica Isolates Based on HSP70Gene
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Leishmaniasis is one of the important parasitic diseases, affecting mainly low social class people indeveloping countries, and is more prevalent and endemic in the tropical and subtropical regions of old worldand new world. Despite ofbroad distribution in Iraq,little known about the geneticcharacteristics of thecausative agents. So this study was aimed to evaluate the genetic varietyoftwo IraqiLeishmaniatropicaisolatesbased on heat shock protein gene sequence 70 (HSP70) in comparison with universal isolates recordedsequences data. After amplification and sequencing of HSP70 gene,the obtainedresults were alignment alongwith homologous Leishmania sequences retrieved from NCBI by using BLAST. The analysis results showedpresence of particular g

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Publication Date
Fri Apr 15 2022
Journal Name
Indian Journal Of Ecology
Antibacterial Activity of Laurus nobilis Leaves Extract against Pseudomonas aeruginosa
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The aim of this study is to evaluating the antibacterial activity of Laurus nobilis leaves extract in hospital environment isolates. Maceration and Soxhlet apparatus were used to prepare aqueous and methanolic extracts. The total phenolic content and high-performance liquid chromatography (HPLC) were conducted to determine the active compounds in the extracts. The results showed that the methanolic and aqueous extracts contain four flavonoids derivatives (kaempferol, luteolin, quercetin and Rutin) were identified on the basis of matching retention time with the standards. The total phenolic contents were 56.81 and 81.56 mg/g in 50 mg/ml, in aqueous and methanolic extracts respectively. The antibacterial activity of Laurus nobilis leaves ext

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Publication Date
Wed Jul 17 2024
Journal Name
Central Asian Journal Of Medical And Natural Sciences
Understanding of the Immunological Tolerance Mechanisms Underlying the Maternal-Fetal
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Publication Date
Wed Apr 30 2025
Journal Name
Iraqi Journal Of Science
Numerical Simulation of Solar Granulation Dynamics Using Optical Correction Techniques
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High-resolution imaging of celestial bodies, especially the sun, is essential for understanding dynamic phenomena and surface details. However, the Earth's atmospheric turbulence distorts the incoming light wavefront, which poses a challenge for accurate solar imaging. Solar granulation, the formation of granules and intergranular lanes on the sun's surface, is important for studying solar activity. This paper investigates the impact of atmospheric turbulence-induced wavefront distortions on solar granule imaging and evaluates, both visually and statistically, the effectiveness of Zonal Adaptive Optics (AO) systems in correcting these distortions. Utilizing cellular automata for granulation modelling and Zonal AO correction methods,

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Scopus Crossref
Publication Date
Sun Dec 01 2002
Journal Name
Iraqi Journal Of Physics
THE THERMOELECTRLC POWER OF THE MAGNETLC Fe-Mn-Al COMPOUNDS
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The thermoelectric power as a function of temperature for the Iron-Manganese-Aluminum, Fe-Mn-Al, alloys for manganese concentrations 0.04, 0.06, 0.08, 0.10 and 0.20 have been investigated in the temperature range 300 K. to 500 K. these results showed that the thermoelectric power coefficient in hot probe measurements showed that the electrons are the majority charge carriers in these alloys.

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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Engineering
Robustness Assessment of Regional GNSS Geodetic Networks for Precise Applications
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Over the past few decades, the surveying fieldworks were usually carried out based on classical positioning methods for establishing horizontal and vertical geodetic networks. However, these conventional positioning techniques have many drawbacks such as time-consuming, too costly, and require massive effort. Thus, the Global Navigation Satellite System (GNSS) has been invented to fulfill the quickness, increase the accuracy, and overcome all the difficulties inherent in almost every surveying fieldwork. This research assesses the accuracy of local geodetic networks using different Global Navigation Satellite System (GNSS) techniques, such as Static, Precise Point Positioning, Post Processing Kinematic, Session method, a

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Publication Date
Wed May 17 2023
Journal Name
Journal Of Engineering
Design of a Differential Chaotic on-off keying communication system
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Among the available chaotic modulation schemes, differential chaos shift keying (DSCK) offers the perfect noise performance. The power consumption of DCSK is high since it sends chaotic signal in both of 1 and 0 transmission, so it does not represent the optimal choice for some applications like indoor wireless sensing where power consumption is a critical issue. In this paper a novel noncoherent chaotic communication scheme called differential chaos on-off keying (DCOOK) is proposed as a solution of this problem. With the proposed scheme, the DCOOK signal have a structure similar to chaos on-off keying (COOK) scheme with improved performance in noisy and multipath channels by introducing the concept of differential coherency used in DCS

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Crossref
Publication Date
Fri Dec 01 2017
Journal Name
Indian Journal Of Natural Sciences
Effect of Differences Pretreatment for Bioethanol Production from Corncobs Substrate
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