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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.

Scopus Clarivate Crossref
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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
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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Crossref
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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Crossref
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
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 Jun 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetic Study and Simulation of Oleic Acid Esterification in Different Type of Reactors
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Esterification reaction is most important reaction in biodiesel production. In this study, oleic acid was used as a suggested feedstock to study and simulate production of biodiesel. Batch esterification of oleic acid was carried out at operating conditions; temperature from 40 to 70 °C, ethanol to oleic acid molar ratio from 1/1 to 6/1, H2SO4 as the catalyst 1 and 5% wt of oleic acid, reaction time up to 180 min. The optimum conditions for the esterification reaction were molar ratio of ethanol/oleic acid 6/1, 5%wt H2SO4 relative to oleic acid, 70 °C, 90 min and conversion of oleic 0.92. The activation energy for the suggested model was 26625 J/mole for forward reaction and 42189 J/mole for equilibrium constant. The obtained results s

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Study of in vitro and in vivo free radical scavenging activity for radioprotection of cerium oxide nanoparticles
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Nanoceria have shown numerous unique characteristics, such as biocompatibility and are excellent agents for biological applications. The aim of this study is to investigate cerium oxide nanoparticles for 2, 2- diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity and their ability to offer protection against ionizing radiation. In vitro antioxidant activity study of nanoceria particles has shown good free radical scavenging activity for DPPH radical assayed within a concentration range of 0.01 to 0.05 g/l, at higher concentrations of nanoparticles showed reverse trend in absorbance and inhibition indicating this finite rang of concentration is suitable for scavenging free radicals, also nanoparticles were found to ha

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Crossref (6)
Crossref
Publication Date
Thu Feb 01 2018
Journal Name
Research Journal Of Pharmaceutical,biological And Chemical Sciense
correlation of serum tumor necrosis factor alpha and high sensitive c-reactive protein with clinical periodontal parameters in osteoarthritis patients
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Publication Date
Mon Mar 15 2021
Journal Name
Al-adab Journal
Alienation in Scapegoat novel by Elie Amir
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 تهدف هذه الدراسة إلى بحث ظاهرة الاغتراب في رواية " ديك الفداء " لايلي عامير ، لأن هذه الظاهرة تبدو أكثر وضوحا في هذه الرواية ، وتمثل تیارا مسيطرة على معطياتها واتجاهاتها الفكرية والفنية، خاصة أن الكاتب استطاع أن يجسد هذه الظاهرة المحورية تجسيدا فنيا متميزا ، وكشف عن طبيعة العلاقة بين عالم الواقع وعالم الحلم لدى الشخصيات، وعما تتسم به من تناقض و تعارض وتصادم و شعور بالإحباط والضياع والاغتراب. وقد اشتملت ال

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Publication Date
Tue Jan 01 2019
Journal Name
Lambert
The concept of Evil in J.R.R.Tolkien Novel Lord of the Rings
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Evil pervades the narrative scene in Tolkien. Hence; his major themes in The Lord of the Rings are shown to be the Evil Nature of Power, the Tyranny of Technology and War as a Destructive Agent. Evil is not as powerful as good. The Boethian conception of evil comes through evil beings such as Melkor Morgoth in The Silmarillion or Sauron ,who cannot do good things but only pervert or mock things; In The Lord of the Rings; Tolkien seems to suggest that there is no absolute evil. The other conception of evil is the Manichaen, a conception which receives more emphasis in Tolkien's trilogy and which sees the world as a battle-ground for warring forces of good and evil. Tolkien frequently personifies the Ring as if it were acting with a will of i

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