Investigation of The Effect of Acylthiourea Derivatives on Diabetes-Associated Enzymes
Nural Yahya
One of the most prevalent chronic metabolic disorders, diabetes mellitus, is defined by chronic hyperglycemia and the emergence of microvascular and macrovascular pathology unique to diabetes. Several diabetes problems are primarily caused by persistent hyperglycemia. In this study, aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were purified using chromatographic techniques from sheep kidneys and alpha-glycosidase purchased commercially. The inhibitory effect of seven acylthiourea compounds on the activity of these enzymes associated with diabetes was investigated. As a result of the studies, the acyl thioureas showed an inhibition effect at the micromolar level on the activity of studied enzymes. The most active compound dimethyl 1-((4-methoxybenzoyl)carbamothioyl)-5,5-di...
1,4-Naphthoquinone thiazole urea hybrids bearing morpholine/piperazine: synthesis, crystal structure, aldose reductase and α-glycosidase enzyme inhibition, molecular docking, and electrochemical interaction with dsDNA
Efeoglu, Cagla | Nural, Yahya
In this study, new 1,4-naphthoquinone thiazole urea hybrids bearing morpholine (3a-d) or piperazine (3e-h) moiety were synthesized in 76-89 % yields and characterized by 1H NMR, 13C NMR, FT-IR, HRMS, and elemental analysis. The stereochemistry of 3d was determined by single crystal x-ray diffraction study. We evaluated the inhibitory potential of these compounds 3a-h on aldose reductase (ALR2) and alpha-glycosidase enzyme (alpha-GLY) activity. Our results indicate that these compounds substantially inhibit ALR2 at micromolar doses, with inhibition constants (KIs) between 0.79 and 2.20 mu M and inhibit alpha-GLY KI between 0.67 and 2.82 mu M. Molecular docking simulations were utilized to elucidate inhibitory effects and establish structure-activity relationships for the synthesized compoun...
Synthesis, Enzyme Inhibition, and Acid Dissociation Constant of 1,4-Naphthoquinone Thiazole Hybrid
Nural, Yahya
In this study, N-((Z)-4-((3r,5r,7r)-adamantan-1-yl)-3-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2yl)thiazol-2(3H)-ylidene)-2,6-difluorobenzamide 3 was synthesized as a new 1,4-naphthoquinone thiazole hybrid compound by reaction of naphthoquinone acyl thiourea compound 2 with 1-((3r,5r,7r)-adamantan-1-yl)-2-bromoethan-1-one in 74% yield and its molecular structure was characterized by various analytical techniques such as 1H/13C NMR, FT-IR, and HRMS. The inhibition effect of the synthesized compound on butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoenzymes (hCA I and hCA II) was investigated. The product 3 showed varying degrees of inhibition 89.92 ± 10.47 nM (against hCA I), 51.60 ± 5.37 nM (against hCA II), 68.11 ± 6.58 nM (against AChE), and 126...
Analytical Methods for Determination of Antiviral Drugs in Different Matrices: Recent Advances and Trends
Viruses are the main pathogenic substances that cause severe diseases in humans and other living things. They are among the most common microorganisms, and consequently, antiviral drugs have emerged to prevent and treat viral infections. Antiviral drugs are an essential drug group considering their prescription and consumption rates for different diseases and indications. Therefore, it is crucial to develop accurate and precise analytical methods to detect antiviral drugs in various matrices. Chromatographic techniques are used frequently for the quantification purpose since they allow simultaneous determination of antivirals. Electrochemical methods have also gained importance since the analysis can be performed quickly without the need for pretreatment. Spectrophotometric and spectrofluo...
New naphthoquinone thiazole hybrids as carbonic anhydrase and cholinesterase inhibitors: Synthesis, crystal structure, molecular docking, and acid dissociation constant
Efeoğlu, Çağla | Selçuk, Özge | Demir, Bünyamin | Nural, Yahya
In this study, N-[3-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-R-thiazol-2(3H)-ylidene]-2,6-difluorobenzamide derivatives as new 1,4-naphthoquinone thiazole hybrids were synthesized by reacting of N-[(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2-yl)carbamothioyl]-2,6-difluorobenzamide with various α-bromoketones in 76–92% yields. Their molecular structures were characterized by 1H NMR, 13C NMR, 19F NMR, FT-IR, and HRMS, and the stereochemistry of one of the hybrids was determined by single crystal x-ray diffraction study. These synthesized new compounds (3a–e) were found to be effective inhibitor molecules for cholinesterases (butyrylcholinesterase (BChE) and acetylcholinesterase (AChE)), and carbonic anhydrase I and II (hCA I and hCA II) enzymes. KI values were found to be in the range...
New 1,2,3-triazole derivatives as acetylcholinesterase and carbonic anhydrase inhibitors: Synthesis, molecular docking, and solubility
Efeoglu, Cagla | Yabalak, Erdal | Nural, Yahya
In this study, a series of new 1,2,3-triazole derivatives were synthesized in 84-93 % yield using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry and characterized by 1H/13C NMR, FT-IR, and HRMS analyses. The synthesized compounds (4a-h) were evaluated for their inhibitory activities against human carbonic anhydrase isoforms I and II (hCA I and hCA II) and acetylcholinesterase (AChE), which are clinically relevant targets in neurological and metabolic disorders. Among them, compounds 4f and 4g exhibited the most potent dual inhibitory activities. Compound 4f showed KI values of 144.30 nM for hCA II and 205.10 nM for AChE, while compound 4g exhibited KI values of 239.10 nM for hCA II and 125.90 nM for AChE. These values demonstrate that 4f and 4g are more effective than ...