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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 Jul 20 2020
Journal Name
Biochemical And Cellular Archive
DETERMINATION OF POLYMORPHISM OF GLUTATHIONE S TRANSFERASE (GST) IN THE IRAQI (DIABETIC AND NON-DIABETIC) ACROMEGALIC PATIENTS
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In Iraqi patients with acromegaly the present investigation included 40 control group and 70 patients with acromegaly divided 35 patients with Diabetic while another 35 patients without Diabetic, with ages between (29-72) years for the identification of GST activity polymorphisms by present and absent GSTM1, GSTT1, and PCR-RFLP, enzymatic digestions were carried out using BsmAI (Biolabs. England, UK) for GSTP1b and AciI (Biolabs, England, UK) for GSTP1c.the association GSTActivity with GST genotype were investigated in a cohort of Iraq acromegaly patients comparing with the healthy control group. The results show a non-significant change in GSTP1b gene in both groups, while show high significantly in GSTP1c in diabetic and non-diabetic acro

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Publication Date
Wed May 03 2017
Journal Name
Petroleum Science And Technology
Investigation of non-Newtonian flow characterization and rheology of heavy crude oil
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Publication Date
Sun Dec 27 2020
Journal Name
Journal Of The College Of Education For Women
Using the Image in Teaching Arabic Language Vocabulary to Non-Native Speakers: The Experience of the Arabic Language Institute - King Abdul-Aziz University - as a Model: آمال موسى عباس الإمام
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The study aims to demonstrate the importance of instructional methods in teaching Arabic language as a second language or teaching the Arabic language to non-native speakers. The study is in line with the tremendous development in the field of knowledge, especially in the field of technology and communication, and the emergence of many electronic media in education in general and language teaching in particular. It employs an image in teaching vocabulary and presenting the experience of the Arabic Language Institute for Non-Speakers-King Abdul-Aziz University. The study follows the descriptive approach to solve the problem represented by the lack of interest in the educational methods when teaching Arabic as a second language. Accordingl

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Publication Date
Tue Jun 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
Effect of phosphorous and amino acid on growth and yield of pea
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Publication Date
Wed Oct 28 2020
Journal Name
Egyptian Journal Of Chemistry
Inhibition of Aluminum Alloy 7025 in Acid Solution Using Sulphamethoxazole
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Corrosion behavior of aluminum alloy 7025 was investigated in hydrochloric acid (pH=1) containing 0.6 mol.dm-3 NaCl in the existence and absence of diverse concentrations of sulphamethoxazole as environmentally friendly corrosion inhibitor over the temperature range (298-313)K. Electrochemical polarization method using potentiostatic technique was employed. The inhibition efficiency has been raised with increased sulphamethoxazole concentration but lessened at temperature increases. The highest efficiency value was 96.5 at 298 K and 2 x10-4 mol.dm-3 concentration of sulphamethoxazole. The sulphamethoxazole adsorption was agreed with Langmuir adsorption isotherm. Some thermodynamic parameter (△Gads) and activation energy (Ea) were determin

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Publication Date
Sat Mar 01 1997
Journal Name
Polymer-plastics Technology And Engineering
Feasibility of Dynamic Acid Corrosion Control in Oil Well Tubing
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Publication Date
Mon Dec 02 2013
Journal Name
International Journal Of Pharmacy And Pharmaceutical Sciences
Formulation and in vitro evaluation of rosuvastatin calcium niosomes
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Publication Date
Wed Jan 01 2020
Journal Name
International Journal Of Pharmaceutical Research
Spectrophotometric Evaluation of Paracetamol in Bulk and Pharmaceutical Preparations
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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and In-vitro Evaluation of Itraconazole Floating Microparticles
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Itraconazole (ITZ) is an antifungal drug (BCSII) used for the treatment of local and systemic fungal infections. Furthermore, ITZ used as an antifungal prophylaxis for immunocompromised patients.

The objective of the study is to overcome the two problems of low and pH dependent solubility of ITZ by its preparation as floating microparticles.

Firstly, pH-dependent floating microparticles were prepared using oil in water solvent evaporation method, from which the best one (F7) selected as a best pH-dependent formula with composition of   ITZ (200mg),EC (800mg), HPMC 15cps (200mg) and safflower oil (2ml) .Then, F7 was compared with the selected Relatively pH-independent ITZ floating microparticles formula  wit

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Publication Date
Tue Jun 15 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation
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Selexipag is an orally selective long-acting prostacyclin receptor agonist, which indicated for the treatment of pulmonary arterial hypertension. It is practically insoluble in water ( class II, according to BCS). This work aims to prepare and optimized Selexipag nanosuspensions to achieve an enhancement in the in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of nanosuspension, and the effect of formulation parameters (stabilizer type, drug: stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size and polydispersity index were studied. SLPNS prepared with Soluplus® as amain stabilizer (F15) showed the smallest particle size 47nm wi

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