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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
Wed Jan 01 2020
Journal Name
Research Journal Of Pharmacy And Technology
Structural, Spectral and Thermal studies of new bidentate Schiff base ligand type (NO) derived from Mebendazol and 4-Aminoantipyrine and it's metal complexes and evaluation of their biological activity
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Publication Date
Sun Mar 17 2019
Journal Name
Baghdad Science Journal
Spectrophotometric Determination of Chlorpromazine Hydrochloride Using 4-Nitroanilline by Oxidative Coupling Reaction
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A simple, rapid spectrophotometric method has been established for the determination of chlorpromazine hydrochloride (CPZ) in its pure form and in a tablet formulations. The  suggested  method  is  based  on  the  oxidative coupling  reaction  with4-nitroainlline using KIO3 in acidic solution to produce a violet colored product with maximum absorption at λ=526 nm.The  analytical data  obtained  throughout  this  study  could  be  summarid  as  follows:  1ml of 1M HCl (pH=2.2), 1 ml  of  4-nitroanilline (1x10-2M), and 1.5ml  of (1x10-2)KIO3 per 25 ml reaction medium. The order of a

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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 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
Wed Jul 05 2023
Journal Name
Pharmacia
Evaluation the anti-inflammatory effect of Omega 369 against acetaminophen-induced hepatotoxicity in mice
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Background: Acetaminophen (N-acetyl-para-aminophenol, or APAP) poisoning, whether intentional or accidental, is a major general health problem, with its toxicity prevalence significantly increasing in many countries. Currently, acetaminophen is considered one of the main causes of acute liver failure globally.

Aim: The aim of this study was to evaluate the possible hepatoprotective effect of Omega-3,6,9 against acetaminophen-induced hepatotoxicity in albino male mice.

Methods: Thirty-five albino male mice were randomly divided into five groups: Group 1 (the negative control) received liquid paraffin orally at a dose of 10 ml/kg for t

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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
Identification of Cladosporium sp. Fungi by in- silico RFLP-PCR
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Cladosporium sp. plays an important role in human health, it is one of the pathogenic fungi which cause allergy and asthma and most frequently isolated from airborne spores.  In this study, a couple of universal PCR primers were designed to identify the pathogenic fungi Cladosporium sp. according to conserved region 5.8S, 18S and 28S subunit ribosomal RNA gene in Cladosporium species. In silico RFLP-PCR were used to identify twenty-four Cladosporium strains. The results showed that the universal primer has the specificity to amplify the conserved region in 24 species as a band in virtual agarose gel. They also showed that the RFLP method is able to identify three Cladosporium spe

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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
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Mixed Ligand Complexes of quinoline-2-carboxylic acid and 4,4/-dimethyl-2,2/-bipyridyl with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV)
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A new mixed ligand complexes were prepared by reaction of quinoline -2-carboxylic acid (L1) and 4,4?dimethyl-2,2?-bipyridyl (L2) with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV) ions. These complexes were isolated and characterized by (FT-IR) and (UV-Vis) spectroscopy, elemental analysis, flame atomic absorption technique, thermogravimetric analysis, in addition to magnetic susceptibility and conductivity measurements. Most complexes were mononuclear and with octahedral geometry, except Cd (II) with tetrahedral geometry, and V (IV) with square pyramidal geometry. A theoretical treatment of the ligands and the prepared complexes in gas phase was done using two programs Hyperchem.8 and Gaussian program (GaussView Currently Available Versions (

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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
Tue Jul 11 2023
Journal Name
Journal Of Educational And Psychological Researches
Content Assessment of the Sciences Textbooks of Grades (1-4) in the Light of International Standards in Mathematics and Science TIMSS 2019 (Cognitive Process Dimension)
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The current research aims to determine the requirements of Trends of International Mathematics and Science Study (TIMSS 2019) and to find out the extent to which the content of science textbooks for grades (1-4) in the Sultanate of Oman includes the requirements of (TIMSS 2019). Only the Cognitive Process dimension has been considered when conducting the analysis. The study population includes all science books from the first to the fourth grade for the academic year 2021-2022. The study identified and organized the requirements in the study tool, which is a list of requirements of (TIMSS 2019). After confirming its validity and reliability, the analysis was performed, and data were collected and analyzed statistically using frequencies

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