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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
Fri Jun 30 2017
Journal Name
Acta Crystallographica Section E Crystallographic Communications
Crystal structure of (<i>E</i>)-4-benzylidene-6-phenyl-1,2,3,4,7,8,9,10-octahydrophenanthridine
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The preparation of the title compound, C26H25N, was achieved by the condensation of an ethanolic mixture of benzaldehyde, cyclohexanone and ammonium acetate in a 2:1:1 molar ratio. There are two crystallographically independent molecules in the asymmetric unit. The two cyclohexyl rings adopt ananti-envelope conformation with the benzyl moiety adopting acisconformation with respect to the nitrogen atom of the phenanthridine segment. In the crystal, molecules are linked through C—H...N interactions into hydrogen-bonded chains that are further arranged into distinct layers by weak offset π–π interactions.

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Publication Date
Sun Jun 02 2013
Journal Name
Baghdad Science Journal
Synthesis and Spectral Studies of Co(II),Ni(II),Zn(II) and Cd(II) Complexes with Ligand 2-[4- Carboxy methyl phenyl azo] -4,5-diphenyl imidazole (4CMeI)
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A new chelate complexes of Co(II),Ni(II),Zn(II) and Cd(II) were prepared by reacting these ions with the ligand 2-[4- Carboxy methyl phenyl azo]-4,5-diphenyl imidazole (4CMeI) The preparation were conducted after fixing the optimum conditions such as (pH) and concentration .UV- visible spectra of these complex solutions were studied for a range of (pH) and concentration which obey lampert-Beers Law.The structures of complexes were deduced according to mole ratio method which were obtained from the spectroscopic studies of the complex solutions .The ratios of metal: ligand obtained were (1:2) for all complexes..(UV-Vis) absorption spectra and The infrared spectra of the chelating complexes were studied ,this may indicate that coordination be

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of a novel coating material on the microleakage of glass hybrid restoration in primary teeth – An in vitro study
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the therm

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Publication Date
Wed Mar 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of a novel coating material on the microleakage of glass hybrid restoration in primary teeth – An in vitro study
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
Evaluation of the cytotoxic effects of the colchicine compound isolated from the leaves of Calotropis procera (Ait) against MCF-7 and SK-GT-4 cancer cell lines.
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Alkaloids are regarded as important nitrogen-containing chemical compounds that serve as a rich source for discovering and developing new drugs where most plant-origin alkaloids have antiproliferation effects on different kinds of cancers. Alkaloids’ continence of Calotropis procera leaves are detected by two biochemical alkaloid reagents. Also GC-MS analysis for leaf alkaloid extract was done that showed the existence of one type of alkaloid compound at retention time12.8min detected as colchicine (C22H25N06( by comparing it with colchicine standard reference (Sigma Aldrich) with M.wt 399g/mol and percentage area 7.1%. Furthermore, identification, separation, and purification

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Antibacterial Activity of bis Heterocyclic Derivatives of 1,3,4-thiadiazole
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The Chemistry of heterocyclic sulphur and nitrogen containing compounds have a great role in the  field of scientific studies, The 2-amino 5-mercapto-1,3,4-thiadiazole ring for instance, has gained more importance in recent years because  they are considered as potent biologically active nucleus. In this study disulfide derivative can be obtained by oxidation with hydrogen peroxide of thiol group of the heterocyclic 2-amino 5-mercapto-1,3,4-thiadiazole ring to obtain compound (3) with expected antibacterial  activity. In order to use it as a diazo component to prepare some new bis azo compounds as possible antibacterial  agents, the reaction of two primary amino groups on both sides of disulfide dimer with sodium nitr

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Publication Date
Sun Dec 30 2018
Journal Name
Baghdad Science Journal
Synthesis and study of biological activity of some new Imidazole derivatives
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In this work ester derivatives were synthesized by the reaction of imidazole derivatives (C1) with ethylchloroacetate in ethanol and NaOH to give the corresponding (C2) .While compound (C3) acetohydrazide was synthesized by the reaction of ester derivatives (C2) with hydrazine hydrat in ethanol. Compound (C3) from the reaction with different aromatic aldehydes in absolute ethanol gave the Schiff′s bases (C4,C5). The product compounds were characterized by FT-IR, U.V and 1HNMR spectra and the biological activities were studied as antibacterial.

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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Serum Tumor Necrosis Factor Alpha and High Sensitive C-Reactive protein as Biomarkers in Periodontitis in Iraqi Patients with Osteoarthritis
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Background: Periodontitis (PD) is well-known chronic disease affecting the periodontal ligament and alveolar bone, Osteoarthritis (OA) is a chronic joint disease with compound reasons characterized by synovial inflammation, subchondral bone remodeling, also the formation of osteophytes, that cause cartilage degradation. Chronic periodontitis and osteoarthritis are considered widely prevalent diseases and related to tissue destruction due to chronic inflammation in general health and oral health. The aim of this study is todetermine the association of chronic periodontitis and osteoarthritits in patients by analysing tumor necrosis factor alpha TNFα and high sensitive c-reactive protein (hsCRP) in the serum. Materials and Method: A tot

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Publication Date
Mon Dec 01 2008
Journal Name
Journal Of Economics And Administrative Sciences
السياسة النقدية في العراق بعد 9/4/2003 (الواقع والطموح)
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لا يستطيع كل كائن حي أو كيان اجتماعي أداء دوره الذي يفترض أن يقوم به ما لم يمتلك الوسائل الكافية والضرورية لأداء ذلك الدور قال سبحانه وتعالى ((قال ربنا الذي أعطى كل شيء خلقه ثم هدى طه 50)).

والنشاط الاقتصادي كجزء من الكيان الكلي للمجتمع لا يختلف عن هذه القاعدة، إذ عندما يراد من النظام الاقتصادي أداء دور فاعل فلا غنى له عن الوسائل التي تمكنه من أداء دوره المنشود. للنظام الاقتصادي مجمو

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Publication Date
Thu Jul 18 2019
Journal Name
Annals Of Tropical Medicine & Public Health
SURVIVIN TARGETING; AN IN SILICO APPROACH FOR ANTICANCER DESIGN
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Survivin, a member of inhibitor of apoptosis family is increasingly used as a target for cancer therapy design because it has a key role in cell growth and inhibition of cell apoptosis. Also it can be used as a biomarker for targeting cancer because it is found in almost all cancer but not normal cells. Our strategy was to design (computationally) a molecule to be used as survivin inhibitor. This molecule was named lead10 and was used furthermore to find (virtually) existing drugs with a good survivin inhibition activity.