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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
Tue May 29 2018
Journal Name
Journal Of Pharmaceutical And Scientific Research
Synthesis and characterization of substituted 1, 2,4-triazole and their derivatives on poly ethylene
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Abstract New derivatives of 1,2,4- triazole , 1,2,4-triazole -3-one and 1,2,4-triazole-3-thione were obtained through this research. Acid hydrazide derivative was present from reaction of poly acryloyl chloride with hydrazine hydrate in presence of DMF as a solvent then reacted with benzonitrile and its derivatives to give 1,2,4-triazole derivatives. After that reaction of poly acryloyl chloride with semicarbazide and semithiocarbazide to form semicarbazone and semithiocarbazone derivatives respectively. Finally, closing of semicarbazone and semithiocarbazone derivatives with 2% NaOH gave 1,2,4-triazole -3-one and 1,2,4-triazole-4-thione derivatives respectively. These new synthesized products have been characterized by infrared, 1 H-n

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Publication Date
Sun Mar 03 2013
Journal Name
Journal Of Al-nahrain University
Synthesis and Characterization of Some New 1,2,3-Triazole, Pyrazolin-5-one and thiazolidinone Derivatives
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Five membered heterocyclics derivatives were synthesized in this work by three routes. The first route includes the synthesis of N-benzoic acid 1,2,3,-triazole derivatives (3),(4) by diazotation of methyl-2-amino benzoate and treating the resulted salt (1) with sodium azide and ethyl acetoacetate or acetyl acetone, respectively. In the second route, derivatives of pyrazole (8) pyrazolin-5-one (9), (10) were prepared by the reaction of the salt (1) with some active methylene compounds to give the corresponding hydrazones derivatives (5-7) which then they were treated with hydrazine hydrate. The third route afforded the synthesis of three derivatives (12), (15a), (15b) of thiazolidinone by two different methods. AII compounds were confirmed b

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Publication Date
Mon Mar 01 2010
Journal Name
Journal Of Kerbala University
Synthesis And Biological Activity Of Some New Compounds Containing 1,2,4-Triazole And Their Derivatives
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Condensation of 1,2- dibromo ethane with para hydroxy benzoic acid gave 1,2-Ethane-bis- 4-oxybenzoic [1]. This Compound was converted with the thionyl chloride to give 1,2-Ethane-bis- 4-oxybenzoyl chloride [2]. Reaction of compound [2] with thiosemicarbizades gave 1,2-Ethanebis[4-oxybenzoyl-thiosemicarbazide] [3] and opteined 1,2-Ethane-bis[3-mercapto-5-phenoxy- 1,2,4-triazole] [4] from treatment compound [3] with NaOH (4%) .The new compounds 1,2- Ethane-bis[3-(substituted thioacyl)-4-(substituted acyl)-5 phenoxy-1,2,4-triazole] [5a-d] and 1,2- Ethane-bis[3-(substituted alkylthio)-5 phenoxy-1,2,4-trizole] [5e-f] derived from compound [4] were synthesized and characterized by physical and spectral data. All the compounds [4], [5a-d] and [5e-

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Publication Date
Tue Mar 30 2021
Journal Name
Iraqi Journal Of Science
Well Log Analysis of Nahr Umr, Shuaiba and Zubair Formations in EB-4 well of East Baghdad Oil Field, Iraq, using Rock Physics Templates (RPTs)
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RPT is a method used for classifying various lithologies and fluids from data of well logging or seismic inversion. Three Formations (Nahr Umr, Shuaiba, and Zubair Formations) were selected in the East Baghdad Oil field within well EB-4 to test the possibility of using this method. First, the interpretations of the well log and Density – Neutron cross plot were used for lithology identification, which showed that Nahr Umr and Zubair formations consist mainly of sandstone and shale, while the Shuaiba Formation consists of carbonate (dolomite and limestone). The study was also able to distinguish between the locations of hydrocarbon reservoirs using RPT. Finally, a polynomial equation was generated from the cross plot domain (AI versus V

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Publication Date
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
Differential Expression of Toll-like Receptor 4 and Nuclear Factor κB of Primary Rat Oral Keratinocytes in Response to Stimulation with<i>Fusobacterium nucleatum</i>
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Publication Date
Thu Nov 02 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Total Sialic Acid Concentrations as a Supporting Marker of Malignancy in Acute Lymphoblastic Leukemia
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To follow  up the  response of  acute  lymphoblastic  leukemic

(ALL)   patients   to   chemotherapy   treatment   and  for   prognosis, diagnosis,  the total Sialic acid  (TSA) levels was studied as a tumor marker. The study included 40 patients (male = 22, female =18) with (ALL)   were   tested   for   the   serum   and   leukocytes   homogenate concentrations  of total sialic acid (TSA)  before and after  treatment with    six   different   chemotherapy   protocols.     &n

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Publication Date
Mon Sep 25 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Spectroscopic Studies of Mixed Catechol-Salicylaldiminate Derivatives of Antimony (III) and Tin (IV)
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MixedØ¢  catechol- Ø¢ salicyladiminenate derivatives of antimony

)

 

(III) and tin (IV) of the general formula M(cate)L"]X, [where:M= Sb, X= Ø¢ 0; Ø¢ M=Sn, Ø¢ X= Ø¢ Cl; Ø¢ cate=catechol; Ø¢ n=l, Ø¢ L=aniline, Ø¢ n=2, Ø¢ L=mآ­ bromo-aniline, n=3, L=p-bromoaniline] were prepared by the reaction of equimolar amount of [(cate)MCln], [where n=l Ø¢ or 2] with Nآ­ arylsalicylaldimines HOC6H4CH=NC6Hs (HL1Ø¢  , HOC6H4CH= NC6H4

 

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Publication Date
Sat Sep 23 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis of some 1,3-diazepine -4,7-diones derivatives (part 2)
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1,3-0xazepine-4)-diones were  prepared by c.ondensation of N­

cinnamylideneareneamines with maleic anhydride,  phthalic;; anhydride

,and  3-nitrophthalic  anhydride.  The  oxazepjne::; were  reacted  with

primary aromatic  amine  to give the corresponding  1 ,3--diazepine-4,7- diones.

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Publication Date
Tue May 06 2014
Journal Name
Plos One
Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats
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The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats.

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Publication Date
Wed Apr 01 2020
Journal Name
International Journal Of Pharmaceutical Research
Synthesis, Characterization, Study the Toxicity and Anticancer Activity of N,O-Chitosan Derivatives
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