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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 Mar 02 2014
Journal Name
Baghdad Science Journal
Exploiting the diazotization reaction of 4- minoacetophenone for Methyldopa determination.
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Based on the diazotization reaction of 4-aminoacetophenone with sodium nitrite in acid medium to form diazonium salt, which was coupled with Methyldopa to form a violet reddish soluble azo dye with maximum absorbance at 560 nm,a batch procedure had been developed for the estamination of Methyldopa. Under optimum experimental parameters affecting on the development and stability of the colored product, Beer´s law obeyed in the range (0.5-45) ?g.ml-1 with a correlation coefficient (0.9979).The proposed method was successfully applied to the determination of Methyldopa in either pure form and in commercial brands of pharmaceuticals, no interference was observed from common excipients in the formulations. The analytical results obtained by app

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Pharmacy Research
Design and in vitro characterization of bisacodyl as a hollow-type suppositories
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Publication Date
Tue May 12 2020
Journal Name
International Journal Of Pharmaceutical Research
Synthesis and Biological Activity of New Imidazaldinone Derivatives
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A research include of synthesized five member ring, which has been synthesized by condensation of 2-(1-(4- hydroxyphenyl) ethylidene)hydrazine-1-carbothioamide[I] with α-chloro ethylacetate in sodium acetate (fused) to form ethyl 2-(4-(1-((4-oxo-2-thioxopyrrolidin-3-ylidene)hydrazono) ethyl)phenoxy)acetate [II]. After that reacted [II]with hydrazine hydrate to resulting compound [III]. Compound [III] was refluxed with 4-aminobenzoicacid in excess of phosphorus oxy chloride give compound [IV],the later compound [IV] interact with acetyl acetone or ethylacetoacetate give to pyrazole and pyrazoline derivatives[V],[VI]. While when reacted with different aromatic aldehydes and one ketone consistence Schiff base derivatives [VII]a-e . The FTIR a

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some New Morpholine Derivatives
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In this paper a new series of morpholine derivatives was prepared by reacting the morpholine with ethyl chloro acetate in the presence triethylamine as a catalyst in benzene gave morpholin-N-ethyl acetate(1) which reacted with hydrazine hydrate in ethanol, and gave morpholin-N-ethyl acetohydrazide (2) . Morpholin-N-aceto semithiocarbazide (3) were prepared by reacting compound(2) with ammonium thiocyanate , concentrated hydrochloric acid and ethanol as a solvent .Compound (3) reacted with sodium hydroxide and hydrochloric acid to give 5-(morpholin-N-methylene)-1H-1,2,4-triazole-3-thiol (4) .The new series of 1,2,4-triazol derivatives (5-8) was synthesized by reaction of compound(4) with formaldehyde , DMF as a solvent and different

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Publication Date
Mon Jun 01 2020
Journal Name
Journal Of Pharmaceutical Sciences And Research
Synthesis and Biological Activity of New Imidazaldinone Derivatives
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A research include of synthesized five member ring, which has been synthesized by condensation of 2-(1-(4- hydroxyphenyl) ethylidene)hydrazine-1-carbothioamide[I] with α-chloro ethylacetate in sodium acetate (fused) to form ethyl 2-(4-(1-((4-oxo-2-thioxopyrrolidin-3-ylidene)hydrazono) ethyl)phenoxy)acetate [II]. After that reacted [II]with hydrazine hydrate to resulting compound [III]. Compound [III] was refluxed with 4-aminobenzoicacid in excess of phosphorus oxy chloride give compound [IV],the later compound [IV] interact with acetyl acetone or ethylacetoacetate give to pyrazole and pyrazoline derivatives[V],[VI]. While when reacted with different aromatic aldehydes and one ketone consistence Schiff base derivatives [VII]a-e . The FTIR a

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Global Pharma Technology
Synthesis and Characterization of Some New Pyrazole Derivatives
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This work contain many steps starting from esterification of isophthalic acid to yield diester compound [I] which was converted to their acid hydrazide [II], then the later compound reacted with ethylacetoacetate to yield pyrazol-5-one compound [III]. Afterword added acetyl chloride to give the compound [IV], thereaction of this compound with theiosemicarbazide ledto produce a new carbothioamide compound [V], Which was reacted with ethyl chloro acetate to yield thethioxoimidazolidin compound [VI]. The condensation reaction of this compound with different substituted aldehyde give new alkene derivatives[VII]a-d. The synthesized compounds were characterized by melting points , FT-IR ,1H-NMR and Mass spectroscopy .

Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some New Benzimidazole Derivatives
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In this paper the new starting material 2-(5-chloro-1H-benzo[d]imidazole-2-yl) aniline (1) was synthesized by the condensation reaction of 4-chloro-o-phenylenediamine and anthranilic acid .The new Mannich base derivatives were synthesized using formaldehyde and different secondary amines to synthesize a new set of benzimidazole derivatives(2-5). Also, the new Schiff-base derivatives (6-10) were synthesized from the reaction of compound (1) with various aromatic aldehydes and the closure-ring was done successfully using mercapto acetic acid to get the new thiazolidine derivatives(11-12).These new compounds were characterized using some physical techniques like:FT-IR Spectra and 1HNMR Spectra.

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Publication Date
Fri Jan 01 2010
Journal Name
Journal Of The College Of Languages (jcl)
§ 4. МЕЖДОМЕТИЯ В ТВОРЧЕСТВЕ В.М.ШУКШИНА И ИХ ИССЛЕДОВАНИЕ.
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Творчество В.М. Шукшина богато междометиями, что замечали многие литературные критики и исследователи языка писателя. В.М.Шукшина считают одним из новаторов в особом использовании разговорной речи как литературного приема. Эту особенность своих произведений комментировал и сам писатель.

Разговорная речь – это разновидность литературного языка, реализующаяся преимущественно в устной форме в ситу

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Publication Date
Tue Jan 01 2013
Journal Name
International Journal Of Advances In Pharmacy, Biology And Chemistry
Synthesis of NSAID with Sulfonamide Conjugates as Possible Mutual Prodrugs using Amino Acid Spacer
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The purpose of this research work is to synthesize conjugates of NSAIDs (ibuprofen, and naproxen) with sulfadiazine as possible mutual prodrugs to overcome the local gastric irritation of NSAIDs with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo bond that undergo reduction only by colonic bacterial azoreductaze enzyme to liberate the parent compound to act locally (treatment of inflammation and infections in colon)

Publication Date
Fri Dec 31 2021
Journal Name
Teikyo Medical Journal
Evaluation of Serum Angiogenic and Anti-angiogenic Markers in Pregnant Women with Placenta Accreta
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Over the last 40 years, rate of cesarean delivery has risen from less than10% to over 30% around the world, and almost simultaneously a 10-foldraise in the incidence of placenta accrete spectrum. Fine coordinationamong vascular endothelial growth factor, soluble fms-like tyrosine kinase1 and placental growth factor is important for normal placentaldevelopment and trophoblast invasion. To measure and compare the levelsof circulating vascular endothelial growth factor, placental growth factorand soluble fms-like tyrosine kinase 1 in pregnant women with placentaaccreta to a control group. A case control study which involved one hundredpregnant females were recruited from the Obstetric ward in BaghdadTeaching Hospital who were pregnant with 28

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