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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
Thu Jan 27 2022
Journal Name
Iraqi Journal Of Science
Cytotoxic Effect of ZnO Nanoparticles on the Viability of Leishmania donovani Promastigotes in vitro
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Leishmaniasis is an endemic disease in Iraq, where both forms of the disease, cutaneous and visceral, are found. The effect of Zinc oxide nanoparticles (ZnO NPs) with mean particle size less than 100 nanometer (nm) on viability and growth rate of Leishmania donovani promastigotes was evaluated. The anti-leishmanial activity of different concentrations (0.1, 0.2, 0.4, 0.6, 0.8, and 1 μg/ml) of ZnO NPs was investigated on promastigotes growth rates and viability in comparison to promastigotes exposed to the same concentrations of sodium stibogluconate (Sb) (pentostam).The inhibitory concentrations (IC50s) of ZnO NPs were calculated after 24 , 48 and 72 hr which were (0.871, 0.156 and 0.120 μg/ml) respectively with significant (p< 0.05

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Publication Date
Wed Feb 08 2023
Journal Name
Iraqi Journal Of Science
Phylogenetic Analysis of Streptomyces spp. Exhibited Different Antimicrobial Activities
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Fourteen isolates were collected from a previous study and all were assigned to be Streptomyces genus, according to physiological and biochemical tests, however all the isolates varied morphologically and exhibited different antimicrobial activity.  All 14 isolates were confirmed Streptomyces by  16S rRNA PCR amplification. Six isolates with high antimicrobial activities were ascertained   Streptomyces spp. by sequencing and phylogenetic analysis. Two isolates among the selected 6 isolates with antimicrobial activity against  E. coli and S. aureus . It recommended to make a complete sequence for 16S  rRNA to detect the  species that

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Microleakage of Pit and Fissure Sealants after Using Different Occlusal Surface Preparation Techniques: An In Vitro Study
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Background: The marginal seal is essential for sealant success because penetration of bacteria under the sealant might allow caries onset or progression. The aim of the present study was to estimate and compare the microleakage of pit and fissure sealant after various methods of occlusal surface preparation. Materials and methods: Thirty non-carious premolars extracted for orthodontic reasons were equally divided into three groups. In group one, occlusal fissures were opened with round carbide bur, in group two, occlusal surfaces of the teeth were cleaned with a dry pointed bristle brush and samples of group three were cleaned with a slurry of fine flour of pumice in water using rubber cup. Then fissures of all teeth were etched using 35% p

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Publication Date
Sat Sep 30 2023
Journal Name
Iraqi Journal Of Science
Investigating the Antioxidant and Apoptosis Inducing Effects of Biologically Synthesized Silver Nanoparticles Against Lymphoma Cells in Vitro
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     The current study aimed to synthesize silver nanoparticles (Ag NPs) in a safe and eco-friendly biological method using green tea extract, characterize them using UV-vis spectroscopy, FTIR, XRD, FESEM, and AFM tools, then investigate their antioxidant potentials against DPPH and their cytotoxicity toward lymphoma cells using MTT and ethidium bromide/propidium iodide dual staining assays, and their genotoxic capacities by assessing their effects on the gene expression of p53, caspase3, bcl-2, and bax genes by qPCR and DNA fragmentation.  Results confirmed the synthesis of silver nanoparticles; the UV-vis results showed a peak of absorbance at 414 nm; FTIR analysis showed absorbance bel

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Publication Date
Mon Jan 29 2018
Journal Name
Iraqi Journal Of Science
Assessment the effect of non-thermal plasma on Escherichia coli and Staphylococcus aureus biofilm formtion in vitro
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Biofilm formation represents one of the biggest problems facing scientists because of this phenomenon linkage with virulence of bacteria and other clinical environmental problems. In the present study, two clinical isolates,
Escherichia coli, and Staphylococcus aureus were exposed to the non thermal plasma for different intervals of time (1, 2, 4, 8, and 16 min). The biofilm was measured post exposing. It was found that 2 min. exposing to non-thermal plasma reduced the biofilm formation by both clinical isolates significantly. It can be concluded that the ability of S. aureus to form biofilm higher than E. coli and exposing for 2 min to non-thermal plasma sufficient to reduce the biofilm formati

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Publication Date
Mon Aug 01 2022
Journal Name
Archives Of Razi Institute
Antimicrobial Effect of Moringa Oleifera L. and Red Pomegranate against Clinically Isolated Porphyromonas gingivalis: in vitro Study
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Moringa oleifera L. and red pomegranate extracts have been reported to inhibit gram-positive facultative anaerobe growth and inhibit the formation of biofilm on tooth surfaces. The current study aimed to assess the antibacterial effect of M. oleifera L. and red pomegranate extracts and their combinations against Porphyromonas gingivalis. The antimicrobial sensitivity, minimum inhibition concentrations (MIC), and minimum bactericidal concentrations after treatment with the aqueous extracts of M. oleifera L. and red pomegranate as well as their combination against clinically isolated P. gingivalis were determined using agar well diffusion and two-fold serial dilution. The anti-biofilm activity of the extracts and their combination was evaluat

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
The Bactericidal Effect of CO2 Laser on Pseudomonas aeruginosa Isolated from Wound and Burn Infections, In-Vitro
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A total of 60 cotton swabs are collected from patients suffering from burn wound and surgical site infections admitted to Baghdad Teaching Hospital and Burn Specialist Hospital in Baghdad city during 9/2013 to 11/2013. All cotton swabs are cultured initially on blood agar and MacConkey agar and subjected for standard bacteriological procedures for bacteriological diagnosis. Twenty samples out of sixty are identified as Pseudomonas aeruginosa by conventional methods. The results of antibiotic susceptibility test illustrate that the antibiotics resistance rate of Pseudomonas aeruginosa isolates is as follows:100% (2020) for ceftriaxone, cefepime and carbencillin, 70% (14/20) for amikacin, 65%(13/20) for tobramycin, ceftazidim and gentamycin,

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Publication Date
Tue Feb 04 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of metal ions release and corrosion potential from different bracket archwire combinations (An in vitro study)
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Background: Esthetic treatment is the options of patient seeking orthodontic treatment. Therefore this study was conducted to measure the concentration of Aluminum, Nickel, Chromium and Iron ions released from combination of monocrysralline brackets with different arch wires immersed in artificial saliva at different duration, to evaluate the corrosion point on different parts of the orthodontic appliances before and after immersion in artificial saliva, and to evaluate the corrosion potential of each group of the orthodontic appliances. Material and methods: Eighty orthodontic sets prepared. Each set represents half fixed orthodontic appliance, from the central incisor to the first molar, for the maxillary arch, each set consisted of molar

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Publication Date
Sat Apr 30 2022
Journal Name
Biomedical Research And Therapy
Association between anti-collagen type II autoantibodies and the acute rheumatoid arthritis phenotype in a cohort of rheumatoid arthritis patients
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Publication Date
Wed Aug 30 2023
Journal Name
Baghdad Science Journal
Hepatocellular Carcinoma Prediction and early Diagnosis of Hepatitis B and C viral infection using miR-122 and miR-223 in a sample of Iraqi patients.
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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Therefore, it is critical for researchers to understand molecular biology in greater depth.  In several diseases including cancer, abnormal miRNA expression has been linked to apoptosis, proliferation, differentiation, and metastasis. Many miRNAs have been studied in relation to cancer, including miR-122, miR-223, and others. Hepatitis B and C viruses are the most important global risk factors for HCC. This study is intended to test whether serum miRNAs serve as a potential biomarker for both HCC and viral infections HBV and C. The expression of miRNA in 64 serum samples was analyzed by RT-qPCR. Compared to healthy volunteers, HCC patients' sera expre

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