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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 Apr 11 2023
Journal Name
Indonesian Journal Of Chemistry
Synthesis of Co (ll), Ni (ll), Cu (ll), Pd (ll), and Pt (lV) Complexes with 14, 15, 34, 35-Tetrahydro-11 H, 31 H-4, 8-diaza-1,3 (3,4)-ditriazola-2,6 (1,4)-dibenzenacyclooctaphane-4,7-dien-15, 35-dithione, and the Thermal Stability of Polyvinyl Chloride Modified Complexes
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In the current endeavor, a new Schiff base of 14,15,34,35-tetrahydro-11H,31H-4,8-diaza-1,3(3,4)-ditriazola-2,6(1,4)-dibenzenacyclooctaphane-4,7-dien-15,35-dithione was synthesized. The new symmetrical Schiff base (Q) was employed as a ligand to produce new complexes comprising Co(II), Ni(II), Cu(II), Pd(II), and Pt(II) metal-ions at a ratio of 2:1 (Metal:ligand). There have been new ligands and their complexes validated by (FTIR), (UV-visible), 1H-NMR, 13C-NMR, CHNS, and FAA spectroscopy, Thermogravimetric analysis (TG), Molar conductivity, and Magnetic susceptibility. The photostabilization technique to enhance the polymer was also used. The ligand Q and its complexes were mixed in 0.5% w/w of polyvinyl chloride in tetrahydrofuran

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Publication Date
Mon Dec 20 2021
Journal Name
Baghdad Science Journal
Recurrent Stroke Prediction using Machine Learning Algorithms with Clinical Public Datasets: An Empirical Performance Evaluation
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Recurrent strokes can be devastating, often resulting in severe disability or death. However, nearly 90% of the causes of recurrent stroke are modifiable, which means recurrent strokes can be averted by controlling risk factors, which are mainly behavioral and metabolic in nature. Thus, it shows that from the previous works that recurrent stroke prediction model could help in minimizing the possibility of getting recurrent stroke. Previous works have shown promising results in predicting first-time stroke cases with machine learning approaches. However, there are limited works on recurrent stroke prediction using machine learning methods. Hence, this work is proposed to perform an empirical analysis and to investigate machine learning al

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Publication Date
Thu Mar 31 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Permeability Prediction in One of Iraqi Carbonate Reservoir Using Hydraulic Flow Units and Neural Networks
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Permeability determination in Carbonate reservoir is a complex problem, due to their capability to be tight and heterogeneous, also core samples are usually only available for few wells therefore predicting permeability with low cost and reliable accuracy is an important issue, for this reason permeability predictive models become very desirable.

   This paper will try to develop the permeability predictive model for one of  Iraqi carbonate reservoir from core and well log data using the principle of Hydraulic Flow Units (HFUs). HFU is a function of Flow Zone Indicator (FZI) which is a good parameter to determine (HFUs).

   Histogram analysis, probability analysis and Log-Log plot of Reservoir Qua

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Publication Date
Sat Jun 28 2014
Journal Name
Iraqi Postgraduate Medical Journal
Comparism Between Transvaginal Cervical Length Measurement and Digital Examination in Prediction of Imminent preterm Delivery
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BACKGROUND: Preterm labour is a major cause of perinatal morbidity and mortality, so it is important to predict preterm delivery using the clinical examination of the cervix and uterine contraction frequency. New markers for the prediction of preterm birth have been developed such as transvaginal ultrasound measurement of cervical length as this method is widely available. OBJECTIVE: To determine, whether transvaginal cervical length measurement predicts imminent preterm delivery better than digital cervical length measurement in women presented with preterm labour and intact membranes. PATIENTS AND METHODS: Two hundred women presented with preterm labour between 24 and 36+6 weeks of gestation were included in this study. All women subjecte

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Publication Date
Tue Oct 01 2019
Journal Name
Journal Of Biotechnology Research Center
Leishmanicidal activity of Artemisinin against cutaneous Leishmaniasis, in Vitro
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Background: Cutaneous leishmaniasis (CL) is a neglected disease in tropical countries, including Iraq. Several studies have sought to examine chemotherapies for leishmaniasis treatment but most of them are of toxic and/or undesirable side effect, therefore, the need for investigating new fewer toxic therapies is essential. Aim of study: In this study, the cytotoxic effect of Artemisinin (ART), a novel herbal compound, was screened against the two forms, promastigotes and amastigotes, of the Iraqi isolate of Leishmania tropica, the causative agent of Baghdad boil. Material and methods:  Different concentrations (1000, 500, 250, 125, 62.5, 31.25, 15.6 and 7.8) µM of Artemisinin were screened to investigate the leishmanic

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Biotechnology Research Center
Leishmanicidal activity of Artemisinin against cutaneous Leishmaniasis, in Vitro
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Background: Cutaneous leishmaniasis (CL) is a neglected disease in tropical countries, including Iraq. Several studies have sought to examine chemotherapies for leishmaniasis treatment but most of them are of toxic and/or undesirable side effect, therefore, the need for investigating new fewer toxic therapies is essential. Aim of study: In this study, the cytotoxic effect of Artemisinin (ART), a novel herbal compound, was screened against the two forms, promastigotes and amastigotes, of the Iraqi isolate of Leishmania tropica, the causative agent of Baghdad boil. Material and methods: Different concentrations (1000, 500, 250, 125, 62.5, 31.25, 15.6 and 7.8) µM of Artemisinin were screened to investigate the leishmanicidal activity of th

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Publication Date
Thu Nov 30 2017
Journal Name
Iosr Journal Of Pharmacy And Biological Sciences (iosr-jpbs)
In-vitro effect of artemisinin on L. tropica promastigotes
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Leishmaniasis is a widespread parasitic disease caused by Leishmania parasite, this disease considers a major health problem among worldwide. Treatments available are expensive or with cytotoxic side effect. This study was aimed to investigate the effect of an herbal new compound, called artemisinin, derived from a Chinese plant called Artemisia annua. Various concentrations were studied in vitro against L. tropica amastigotes by chamber counting to investigate its effect on the proliferation of promastigotes. Three incubation periods were adopted (24, 48, 72) hours. The results showed a significant decrease in surviving promastigotes, in parallel with the normal parasite count of untreated promastigotes, along the periods studied. This stu

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Publication Date
Sun Sep 05 2010
Journal Name
Baghdad Science Journal
Effect of vibrio cholerae enterotoxin on phagocytosis in vitro
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Enterotoxin of Vibrio cholerae was extracted by cooling centrifuge at 6.000 rpm for 30 minntes. and filtrated by using milipore filter (0.22 ?m). The effect of crude enterotoxin on phagocytosis was studied by measuring the phagocytic index for 20 blood sample which were collected from healthy people and treated with enterotoxin in addition to control samples. From the results we found that phagocytic index of blood sample which were treated with enterotoxin was 42.9% while the phagocytic index of control blood samples was 64%. This means that there is a negative effect for the enterotoxin resulted from vibrio choleaa on the activity of phagocytic index.

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Publication Date
Wed Nov 15 2017
Journal Name
Journal Of Pharmacy And Biological Sciences
In-vitro effect of Artemisinin on L. tropica promastigotes
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Leishmaniasis is a widespread parasitic disease caused by Leishmania parasite, this disease considers a major health problem among worldwide. Treatments available are expensive or with cytotoxic side effect. This study was aimed to investigate the effect of an herbal new compound, called artemisinin, derived from a Chinese plant called Artemisia annua. Various concentrations were studied in vitro against L. tropica amastigotes by chamber counting to investigate its effect on the proliferation of promastigotes. Three incubation periods were adopted (24, 48, 72) hours. The results showed a significant decrease in surviving promastigotes, in parallel with the normal parasite count of untreated promastigotes, along the periods studied. Th

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Publication Date
Sat Apr 01 2023
Journal Name
Fluid Phase Equilibria
Prediction of solubility of vitamins in the mixed solvents using equation of state
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