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Synthesis, In Silico, and Biological Evaluation of Non‐Hydroxamate Benzoic Acid–Based Derivatives as Potential Histone Deacetylase Inhibitors (HDACi)
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ABSTRACT<p>Unregulated epigenetic modifications, including histone acetylation/deacetylation mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), contribute to cancer progression. HDACs, often overexpressed in cancer, downregulate tumor suppressor genes, making them crucial targets for treatment. This work aimed to develop non‐hydroxamate benzoic acid–based HDAC inhibitors (HDACi) with comparable effect to the currently four FDA‐approved HDACi, which are known for their poor solubility, poor distribution, and significant side effects. All compounds were structurally verified using FTIR, <sup>1</sup>HNMR, <sup>13</sup>CNMR, and mass spectrometry. In silico analysis showed that compound <bold>A3bn</bold> (3‐chloro‐4‐((2‐(2‐(4‐hydroxybenzylidene) hydrazinyl)‐2‐oxoethyl)amino)benzoic acid) has strong binding affinity towards HDAC2, HDAC6, and HDAC8 and exhibits molecular similarity to trichostatin and SAHA (HDACi). <bold>A3bn</bold> achieved IC<sub>50</sub> values comparable to SAHA against MCF‐7 (20.3 vs. 39.2 µM) and K562 (42.0 vs. 36.1 µM) cancer cells. Western blot analysis confirmed that <bold>A3bn</bold> inhibited H3 and H4 deacetylation. Additionally, <bold>A3bn</bold> induced the extrinsic apoptotic pathway via caspase 8 activation, leading to cell death. Its enhanced activity across HDAC isoforms may result from its hydrophilic linker, facilitating zinc coordination. In conclusion, <bold>A3bn</bold> demonstrated efficacy similar to FDA‐approved HDACi and represents a promising candidate for further optimization. Future studies will focus on structural modifications to enhance potency and selectivity at lower concentrations.</p>
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Publication Date
Mon Oct 01 2018
Journal Name
Conference: First International Conference On Water Resources
Modeling BOD of the Effluent from Abu-Ghraib Diary Factory using Artificial Neural Network October 2018
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The proper operation, and control of wastewater treatment plants, is receiving an increasing attention, because of the rising concern about environmental issues. In this research a mathematical model was developed to predict biochemical oxygen demand in the waste water discharged from Abu-Ghraib diary factory in Baghdad using Artificial Neural Network (ANN).In this study the best selection of the input data were selected from the recorded parameters of the wastewater from the factory. The ANN model developed was built up with the following parameters: Chemical oxygen demand, Dissolved oxygen, pH, Total dissolved solids, Total suspended solids, Sulphate, Phosphate, Chloride and Influent flow rate. The results indicated that the constructed A

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Publication Date
Mon Nov 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Impact Of Adopting The Social Responsibility On Marketing Performance An Applied Study on NAFTAL Company
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This research paper aims at studying the effect of adopting the corporate social responsibility on marketing performance indicators, where the study adopted the descriptive method for theoretical concepts, in addition to the statistical approach by using the SPSS v25 program to analyze the questionnaire and test the hypotheses of the study. The results showed that there is a positive correlation between social responsibility and marketing performance indicators, and the study found that it is better for NAFTAL Company to mix the environmental and social responsibilities in order to improve its marketing performance. Also, the study recommended that Naftal should adopt the four responsibilities equally, correctly and make its work

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Publication Date
Tue Oct 20 2020
Journal Name
International Journal Of Civil Engineering
Structural Performance Under Monotonic Static Loading of Reinforced Concrete Gable Roof Beams with Multiple Web Openings
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Publication Date
Tue May 30 2017
Journal Name
Environmental Earth Sciences
Purification of aqueous solutions from Pb(II) by natural bentonite: an empirical study on chemical adsorption
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Publication Date
Thu Aug 01 2024
Journal Name
Baghdad Science Journal
APR-246 enhances the anticancer effect of doxorubicin against p53-mutant AsPC-1 pancreatic cancer cells
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سرطان البنكرياس هو مرض ذو معدل وفيات مرتفع، ولا يزال التشخيص المبكر لسرطان البنكرياس يمثل تحديًا. يظل معدل البقاء النسبي لمدة 5 سنوات أقل من 8%، والاستراتيجيات العلاجية غير فعالة في زيادة معدلات بقاء المريض على قيد الحياة. في خلايا سرطان البنكرياس، ارتبطت مقاومة العلاج بالتغيرات الجينية التي تؤدي إلى ظهور مسارات خلوية شاذة؛ ولذلك، هناك ما يبرر ايجاد استراتيجيات جديدة لعلاج هذا المرض. هنا، سعينا لاستكشاف

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Publication Date
Mon Apr 01 2024
Journal Name
South African Journal Of Chemical Engineering
Removal of COD from petroleum refinery wastewater by adsorption using activated carbon derived from avocado plant
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Publication Date
Mon Mar 01 2021
Journal Name
Solar Energy
Efficient thermal management of the photovoltaic/phase change material system with innovative exterior metal-foam layer
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Publication Date
Sat Feb 01 2020
Journal Name
Physics Of Fluids
Modeling the effects of slip on dipole–wall collision problems using a lattice Boltzmann equation method
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We study the physics of flow due to the interaction between a viscous dipole and boundaries that permit slip. This includes partial and free slip, and interactions near corners. The problem is investigated by using a two relaxation time lattice Boltzmann equation with moment-based boundary conditions. Navier-slip conditions, which involve gradients of the velocity, are formulated and applied locally. The implementation of free-slip conditions with the moment-based approach is discussed. Collision angles of 0°, 30°, and 45° are investigated. Stable simulations are shown for Reynolds numbers between 625 and 10 000 and various slip lengths. Vorticity generation on the wall is shown to be affected by slip length, angle of incidence,

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Publication Date
Wed Jul 17 2019
Journal Name
Aip Conference Proceedings
The correction of the line profiles for x-ray diffraction peaks by using three analysis methods
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In this study used three methods such as Williamson-hall, size-strain Plot, and Halder-Wagner to analysis x-ray diffraction lines to determine the crystallite size and the lattice strain of the nickel oxide nanoparticles and then compare the results of these methods with two other methods. The results were calculated for each of these methods to the crystallite size are (0.42554) nm, (1.04462) nm, and (3.60880) nm, and lattice strain are (0.56603), (1.11978), and (0.64606) respectively were compared with the result of Scherrer method (0.29598) nm,(0.34245),and the Modified Scherrer (0.97497). The difference in calculated results Observed for each of these methods in this study.

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Publication Date
Wed Mar 01 2023
Journal Name
Journal Of Engineering
Experimental Study on the Behavior of Square-Skirted Foundation Rested on Gypseous soil Under Inclined Load
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This work investigates experimentally the effect of using a skirt with a square foundation of 100 mm width resting on dry gypseous soil (i.e., loose soil with 33% relative density), and subjected to an inclined load. Previous works did not study the use square skirted foundation rested on gypseous soil and subjected to inclined load. The investigated soil was brought from Tikrit city with 59% gypsum content. Standard physical and chemical tests on selected soil were carried out. Model laboratory tests were carried out to determine the effect of using a skirt with a square foundation on the load-settlement behavior of gypseous soil and subjected to inclined load with various Skirt depth (Ds) to foundation width (B) ratio

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