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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
Sat Jun 15 2019
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Antibacterial Activity of Some Novel Schiff S-Bases Compounds Containing Oxadiazole Ring
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Condensation of 4-methoxybenzoyl hydrazine with 4- aminobenzoic acid in the presence of POCl3 gave the oxadiazole derivative [III] .This compound was demethylated with aluminium chloride to give series of 2- (4-hydroxy phenyl)-5-(4-amino phenyl)
1,3,4-oxadiazole [IV]. Series of Schiff s bases [V]n were synthesized by the condensation of compound [IV] with 4-n-alkoxy benzaldehyde in the presence of glacial acetic acid. Condensation of compounds [VI]n.  with adipoyl chloride in dry pyridine leads to the formation of a new homologous series [VI]n. The structures of the synthesized compounds were confirmed by physical and spectral means The new compounds [VI]n have been screened for their antibacterial activities . The results

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Publication Date
Thu Feb 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Antileishmanial Activity of Osteospermum ecklonis Extract of Aerial Parts against Leishmania donovani: in vitro(Conference Paper) #
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Abstract

 

Lack of safe available non-resistant treatment for visceral leishmaniasis (Kala-azar) keeps limiting the complete cure of this disease ,drugs that have  toxic side effects or lack of effectiveness  have led to disease relapse ,all these factors have lightened  the way to the search for imperative drugs from natural resources that have been shown to have antileishmanial activity through literature survey

. In the present study, the comparative in vitro anti-leishmania activity of various fractions of Osteospermum ecklonis aerial parts fractions have been evaluated. Extracts were prepared through maceration and Soxhlet apparatus using 85% meth

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Publication Date
Fri Dec 01 2023
Journal Name
History Of Medicine
A comparative study of integrin- linked kinase 1 and anti-smith antibody as diagnostic biomarkers in Iraqi patients with systemic lupus erythematosus
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Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. Aimes of study determination of integrin- linked kinase 1(ILK-1) and anti-smith antibody(ASAB) levels in serum of Iraqi patients with systemic lupus erythematosus, in addition, that ILK-1 may be as a diagnostic marker of SLE disease, and study the effect of systemic lupus erythematosus on renal function in these patients. This study included 100 females’ patients with systemic lupus erythematosus attending to the Rheumatology Unit in Baghdad Teaching Hospital, Medical City, (Baghdad), in addition to 30 healthy females as controller group were chosen without any chr

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Characterization of New Isatin-Ibuprofen Derivatives with Expected Biological Activity
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Ibuprofen is one of the most important members of NSAIDs, named aryl propionic acid derivative. Isatin (1H-indole-2,3-dione) is an important molecule of heterocyclic compounds that have many biological activities. This work illustrates the synthesis of new ibuprofen-isatin derivatives by connecting ibuprofen hydrazide with different isatin derivatives by a condensation reaction, followed by characterization by fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The anti-inflammatory activity was evaluated by using the egg-white induce edema method for all the synthesized compounds (5-8), the compounds 5 and 6 showed better anti-inflammatory activity than ibuprofen as a standard

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Characterization of New Isatin-Ibuprofen Derivatives with Expected Biological Activity
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Ibuprofen is one of the most important members of NSAIDs, named aryl propionic acid derivative. Isatin (1H-indole-2,3-dione) is an important molecule of heterocyclic compounds that have many biological activities. This work illustrates the synthesis of new ibuprofen-isatin derivatives by connecting ibuprofen hydrazide with different isatin derivatives by a condensation reaction, followed by characterization by fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The anti-inflammatory activity was evaluated by using the egg-white induce edema method for all the synthesized compounds (5-8), the compounds 5 and 6 showed better anti-inflammatory activity than ibuprofen as a standard compoun

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Publication Date
Wed Feb 01 2017
Journal Name
Journal Of Controlled Release
Surface engineering tumor cells with adjuvant-loaded particles for use as cancer vaccines
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Publication Date
Tue Jan 02 2024
Journal Name
Medical Oncology
COX 2-inhibitors; a thorough and updated survey into combinational therapies in cancers
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Publication Date
Thu Jun 26 2025
Journal Name
Journal Of Legal Sciences
A comparative study between the federal investment law No. 13 of 2006 and the Investment Law Kurdistan No. 4 of 2006
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Publication Date
Wed Oct 30 2024
Journal Name
Iraqi Journal Of Science
Evaluation of the Activity of Olibanum Oil as an Immune Booster in Rats
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The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations.  The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well a

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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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