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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
Tue Jun 15 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats
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Abstract

At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats.

Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats ea

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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
The importance of providing Islamic finance services for non- Muslims in Europe
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Abstract

             This paper follows the growing interest and continuity of Islamic finance products worldwide, which has encouraged the formulation of financial institutions based on the concepts of Islamic Sharia in many countries of the world and is no longer limited to Islamic countries only, and  Not exclusive to Muslims which is due to Islamic finance services and their ability to apply in non-Islamic societies, and perhaps what encouraged the development and progress of this industry Islamic history, which was attended by many different models With the development of trade's share between different countries as well as trips carried out by Muslims

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Publication Date
Fri Sep 30 2022
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Evaluation of direct withholding tax procedures as a tool to increase tax proceeds : applied research in the General Tax Authority / Direct Deduction Department
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The research aims to evaluate the direct deduction department’s procedures for the process of collecting income tax using the direct deduction method for state departments and the public sector in light of direct deduction tax instructions No. (1) of 2007 and Income Tax Law No. (113) of 1982 (amended) through Giving a clear idea of ​​the reality of tax collection procedures because this type of tax is one of great importance because it contributes to the provision of financial revenues to the state to finance its expenses and direct the economy towards achieving its social, economic and political goals. The researcher makes comparisons between the procedures of the General Tax Authority in collecting the tax and what was approved b

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Publication Date
Mon Dec 18 2017
Journal Name
Agronomy
A Case Study of Potential Reasons of Increased Soil Phosphorus Levels in the Northeast United States
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Recent phosphorus (P) pollution in the United States, mainly in Maine, has raised some severe concerns over the use of P fertilizer application rates in agriculture. Phosphorus is the second most limiting nutrient after nitrogen and has damaging impacts on crop yield if found to be deficient. Therefore, farmers tend to apply more P than is required to satisfy any P loss after its application at planting. Several important questions were raised in this study to improve P efficiency and reduce its pollution. The objective of this study was to find potential reasons for P pollution in water bodies despite a decrease in potato acreage. Historically, the potato was found to be responsible for P water contamination due to its high P sensitivity a

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Publication Date
Fri Dec 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Oral health status in relation to nutritional status among institutionalized and non-institutionalized orphans in Baghdad city
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Background: Nutritional condition was reported as one of the factors affecting the oral health status, particularly among underprivileged groups. Orphans are one of the known high-risk groups. The aims of this study were to assess the nutritional status of orphans, and its impact on the oral health status. Materials and Methods: Five-hundred children aged 6-12 years old, 254 males and 246 females: institutionalized, non-institutionalized orphans and controls were participated in this study. Nutritional status assessed according to body mass index (BMI). Ramfjord index teeth were examined to assess oral cleanliness and gingival condition. All data were analyzed using SPSS version 23. Results this study revealed the institutionalized orphans

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Publication Date
Tue May 01 2018
Journal Name
Applied Surface Science
Structural, morphological, and optical characterizations of Mo, CrN and Mo:CrN sputtered coatings for potential solar selective applications
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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Analysis of Fatty Acid Composition in the Seed and flower oil of Syrian Ligustrun Lucidum and olive oil
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The fatty acid composition in the seed and flower of Ligustrun lucidum and olive oil was studied by Gas Chromatography. Results showed that the main components of seed oil were Palmitic (C16:0) 5,893% ,Palmitolic acid (C16:1)0,398%, Steaeic (C18:0)2,911% ,Oleic (C18:1)74,984%,Linoleic (C18:2) 12,959%,and Linolenic (C18:3) 0,997%. The proportion of unsaturated fatty acid was above 89,338%, so the seed oil of L. lucidum ait belonged to unsaturated oil which possessed promising application. The components of flower oil were Palmitic (C16:0) 65,674% ,Palmitolic acid (C16:1)6,516%, Steaeic (C18:0)2,641% ,Oleic (C18:1)14,707%,Linoleic (C18:2) 3,113%,and Linolenic (C18:3) 2,70%. The proportion of unsaturated fatty acid and saturated fatty acid wa

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Publication Date
Tue Aug 01 2023
Journal Name
Dna Repair
The interactions between DNA methylation machinery and long non-coding RNAs in tumor progression and drug resistance
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DNA methylation is one of the main epigenetic mechanisms in cancer development and progression. Aberrant DNA methylation of CpG islands within promoter regions contributes to the dysregulation of various tumor suppressors and oncogenes; this leads to the appearance of malignant features, including rapid proliferation, metastasis, stemness, and drug resistance. The discovery of two important protein families, DNA methyltransferases (DNMTs) and Ten-eleven translocation (TET) dioxygenases, respectively, which are responsible for deregulated transcription of genes that play pivotal roles in tumorigenesis, led to further understanding of DNA methylation-related pathways. But how these enzymes can target specific genes in different malignancies;

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Publication Date
Thu Apr 27 2023
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Total L-carnitine and insulin resistance in non-obese and obese Iraqi women with polycystic ovary syndrome
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Background: Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine illnesses affecting reproductive - age women. L-carnitine has important roles in oxidative stress, energy production and glucose metabolism. It affects insulin resistance as decreased plasma carnitine level has been well reported in type II diabetes mellitus. Hence, it means L-carnitine may reduce insulin resistance which is found in PCO disease. Objective: This study aims to measure the level of L-carnitine and insulin resistance in both obese and non- obese patients with PCOS. Patients and Methods: Sixty women within the reproductive age with PCOS (30 obese and 30 non- obese) were recruited from the Gynecology and Obstetrics Outpatient Clinic in Baghdad T

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Publication Date
Mon Jan 01 2018
Journal Name
Biochemical And Cellular Archive
Irrigation intervals affect dhn1 expression and some physiological parameters in stay green and non-stay-green sorghum
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