Esculetin attenuates doxorubicin-induced cardiac toxicity: Evidence from gene expression, enzyme activity, and molecular docking analyses.

Doxorubicin (DOX) is a potent chemotherapeutic agent whose dose-dependent cardiotoxicity is associated with oxidative stress, inflammation, and enzymatic dysfunction. This study evaluates the cardioprotective potential of esculetin, a natural coumarin derivative, against DOX-induced cardiac injury in rats. Forty-eight male Sprague-Dawley rats were divided into six groups, including control, DOX, esculetin (50 and 100 mg/kg), and combination treatments.

Synthesis, Biological Evaluation and Molecular Docking of Novel Sulfonamide Derivatives as Dual Inhibitors of Carbonic Anhydrase Isoenzymes I/II and Acetylcholinesterase.

In this study, a novel series of multifunctional sulfonamide-based compounds (1-9) incorporating aziridine, dithiocarbamate, thiocyanate, and benzo[d]thiazole fragments were synthesized through nucleophilic substitution reactions using N-2,3-dichloropropylbenzenesulfonamide as the key intermediate. The chemical structures of the synthesized compounds were elucidated by spectroscopic techniques including ¹H NMR, ¹³C NMR, and elemental analysis. The inhibitory potentials of the synthesized compounds were assessed against three key enzymes: human carbonic anhydrase isoforms I and II (hCA I and hCA II) and acetylcholinesterase (AChE).

Phenolic Compounds in Exercise Physiology: Dual Role in Oxidative Stress and Recovery Adaptation.

Exercise-induced oxidative stress results from the overproduction of reactive oxygen and nitrogen species (ROS/RNS) during intense physical activity, potentially impairing muscle function and recovery. Phenolic compounds, abundant in plant-based foods, are known for their potent antioxidant properties and may modulate redox homeostasis in athletes. This review critically examines the dual role of phenolic compounds in exercise physiology, highlighting both their protective antioxidant effects and the risks of excessive intake that may disrupt adaptive responses.

New Quinazolin-4(3H)-One-Thiazolidine-2,4-Dione Hybrids as Dual Inhibitors of α-Glycosidase and Aldose Reductase: The Synthetic, In Vitro, and In Silico Approaches.

The impact of diabetes and its complications on individuals is profound, leading to severe health issues and reduced quality of life. This study aimed the design, synthesis, and evaluation of new quinazolin-4(3H)-one-thiazolidine-2,4-dione hybrids as dual inhibitors targeting α-glycosidase (α-Gly) and aldose reductase (ALR2), two key enzymes implicated in type 2 diabetes mellitus (T2DM) and its complications. Thirteen compounds were synthesized and characterized using FTIR, NMR, and HRMS.

Bioinformatics-Based Discovery of Therapeutic Targets in Cadmium-Induced Lung Adenocarcinoma: The Role of Oxyresveratrol.

In this study, we establish a comprehensive bioinformatic and experimental platform for revealing the molecular bases of cadmium (Cd)-induced lung adenocarcinoma (LUAD) and the therapeutic efficacy of the natural polyphenol oxyresveratrol (O-RES) against this disease. A total of 116 differentially expressed genes (DEGs) were obtained, including 30 upregulated and 86 downregulated obtained by integrating five LUAD-related transcriptomic datasets from the GEO database. Results of network analysis identified four core hub genes: upregulated (Mmp9 and Col1a1) and downregulated (Cdh5 and Pecam-1).

Protective Effects of Hispidulin Against Oleic Acid-induced Acute Kidney Injury in Rats: Integrated Enzymatic and Molecular Docking Analysis.

Oleic acid (OA) is the primary monounsaturated free fatty acid that is crucial in animal nutrition, but excessive amounts can cause cell damage. Hispidulin (HIS) is a flavone present in several plants that has diverse pharmacological actions such as anti-adipogenic, anti-inflammatory, antioxidant, anticancer, and antifungal characteristics. During the investigation, 30 adult male Sprague Dawley rats were used.

Antidiabetic properties of dihydrooxazole Derivatives: In vitro and in silico evaluation as potential aldose reductase and α-glucosidase inhibitors.

Proteins included in type 2 diabetes mellitus are potential targets for minimizing the disease progression. In this contribution, fourteen cinnamoyl compounds were synthesized and characterized, leading to five new oxazole derivatives. Their structures were optimized at the B3LYP/6-311++G(d,p) level of theory, and the global and local reactivity parameters were calculated.

Quinazolin-4(3H)-One-Based New Glitazones as Dual Inhibitors of α-Glucosidase and Aldose Reductase: Comprehensive Approaches for Managing Diabetes Mellitus and Its Complications.

A series of novel glitazones containing thiazolidine-2,4-dione and quinazolin-4(3H)-one moieties were synthesized to explore their potential as dual inhibitors of aldose reductase (ALR2) and α-glucosidase (α-Glu), two key enzymes involved in diabetes and its complications. In vitro assays revealed that compounds 8 (cyclohexyl substituted), 9 (phenethyl substituted), and 11 (phenyl substituted) exhibited potent inhibitory effects on both enzymes, with 11 being the most active, showing an ALR2 inhibition (K = 0.106 µM) approximately nine times more effective than the standard epalrestat (EPR) (K = 0.

New 1,2,3-triazole derivatives as acetylcholinesterase and carbonic anhydrase inhibitors: Synthesis, molecular docking, and solubility.

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 H/C 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.

Synthesis of novel pyrazino[1,2-a]indol-1(2H)-one derivatives as potent cholinesterase inhibitors and their in vitro and in silico evaluations.

The development of effective cholinesterase inhibitors remains a critical strategy in the search for novel therapeutics for Alzheimer's disease (AD). In this work, a series of novel 3-substituted pyrazino[1,2-a]indol-1(2H)-one derivatives were rationally designed, synthesized, and fully characterized through comprehensive spectral analyses. The cholinesterase inhibitory activities of the compounds were systematically evaluated, demonstrating potent inhibition against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at nanomolar concentrations.

Development of phenolic Mannich bases as α-glucosidase and aldose reductase inhibitors: In vitro and in silico approaches for managing diabetes mellitus and its complications.

The rising incidence of type 2 diabetes mellitus (T2DM) and its related complications has created an urgent need for new therapeutic approaches. We herein describe the synthesis as well as biological investigation of a series of sixteen new phenolic Mannich base derivatives of thiazolidine-2,4-dione as α-glucosidase (α-Glu) and aldose reductase (ALR2) inhibitors, two crucial enzymes involved in T2DM and its complications. In vitro assays showed strong inhibitory activities, compound 12 (tetrahydroisoquinoline and α-methylcinnamyl substituted) exhibited the strongest inhibition of ALR2 (K: 0.

A new series of naphthyl-thiosemicarbazone and thio/carbohydrazone derivatives: Synthesis, spectroscopic elucidation, dual enzyme inhibition targeting carbonic anhydrase/ acetylcholinesterase and molecular docking studies.

New naphthyl-thiosemicarbazone derivatives (1-9) were obtained from 1-naphthaldehyde and numerous thiosemicarbazides. New naphthyl-thio/carbohydrazones (10-12) were prepared from 1-naphthaldehyde and various thio/carbohydrazides. FT-IR, H NMR, C NMR, and elemental analysis were used to elucidate the structures of the newly obtained compounds.

Design, synthesis, and aldose reductase inhibition assessment of novel Quinazolin-4(3H)-one derivatives with 4-Bromo-2-Fluorobenzene functionality.

Aldose reductase (ALR2) inhibition is a promising therapeutic strategy for managing diabetes-related complications, including neuropathy, retinopathy, and nephropathy. This study reports the design, synthesis, and biological evaluation of eighteen novel quinazolin-4(3H)-one derivatives incorporating a 4-bromo-2-fluorobenzylidene moiety as ALR2 inhibitors. Among the synthesized compounds, the cyclohexyl-substituted derivative (compound 9) exhibited the highest potency as a competitive ALR2 inhibitor, with a K of 0.

Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular docking and Enzymatic Inhibition for Therapeutic Potential.

In this study, a series of new oxirane and thiirane (2a-g), were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). So, in the first stage, 1-chloro-3-phenothiazylpropanol-2 (2), methyl, methoxy-substituted oxirane, thiirane (2a and 2b), methyl, 1,2-aminopropanethiols (2c-2f), trifluorinated aminethiol derivative (2g), have been synthesized. The structures of synthesized compound were confirmed by IR, NMR analysis.

Isoindole-1,3-Dione Sulfonamides as Potent Inhibitors of Glucosidase, Aldose Reductase, and Tyrosinase: A Molecular Docking and Enzyme Inhibition Study.

Diabetes mellitus, especially type 2, is a global health challenge, and effective enzyme inhibitors are essential for its control. Conventional inhibitors have drawbacks such as gastrointestinal side effects and regional availability, examples being acarbose and epalrestat. Moreover, tyrosinase, which controls melanin synthesis which is also a target for reducing hyperpigmentation disorders.

Determination of the Inhibitory Potential of Chalcones on Myeloperoxidase Enzyme Activity: In vitro and Molecular Docking Studies.

Myeloperoxidase (MPO) is a highly abundant hemoprotein in neutrophils and monocytes. It has a crucial function in immunological surveillance and the body's defensive systems. Nevertheless, there is a strong correlation between elevated MPO activity and the development and advancement of inflammatory processes.

Design, synthesis, and inhibition of α-glucosidase by novel l-phenylalanine-derived hydrazones: Kinetic, molecular docking, and dynamics studies.

In this paper, a series of novel hydrazones derived from L-phenyl alanine were synthesized in four steps and employed to inhibit α-glucosidase through kinetic studies, molecular docking, and molecular dynamics analyses. Among the synthesized compounds, 8, 15, and 16 exhibited the strongest inhibitory effects, with IC values of 31.08 μM, 24.

Chemical Composition, Antimicrobial, and Enzyme Inhibitory Properties of Elaeagnus angustifolia L.

Research on natural antioxidants derived from plants has surged due to their potential health benefits. In the current study, the chemical composition, enzyme inhibitory activity, and antimicrobial effects of the Elaeagnus angustifolia L. plant, including leaves, flowers, and flower stalk (FS) extracts, were analyzed.

Novel Schiff Base Sulfonate Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Docking Insights.

Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization of six novel Schiff base sulfonate derivatives (L-L) through spectroscopic techniques (FT-IR and NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE), which are crucial therapeutic targets for diseases such as glaucoma, epilepsy, and Alzheimer's disease.

Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and Studies.

The new dibenzoazepine-substituted triazole hybrids (-) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. The hybrid structures (-) were obtained in high yields (74-98%) with a simple two-step synthesis strategy and fully characterized. These compounds were assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE).

Novel benzenesulfonamides containing a dual triazole moiety with selective carbonic anhydrase inhibition and anticancer activity.

A series of sulfonamides incorporating a 1,2,3-triazolyloxime substituted 1,2,3-triazolyl moiety were conceptualized and synthesized as human carbonic anhydrase (CA) inhibitors. The synthesized small structures, denoted 7a through 7o, exhibited moderate inhibitory effects against the tumor-associated isoforms CA IX and CA XII compared to the well-known CA inhibitor acetazolamide. In contrast, these molecules demonstrated higher potency and a diverse range of selectivity against the cytosolic isoforms CA I and CA II.

Synthesis of N-substituted 4-phenyl-2-aminothiazole derivatives and investigation of their inhibition properties against hCA I, II, and AChE enzymes.

In this study, thiazole derivatives containing sulphonamide, amide, and phenyl amino groups were synthesized to protect the free amino groups of 5-methyl-4-phenyl-2-aminothiazole and 4-phenyl-2-aminothiazole. Halogenated reactions of N-protected thiazole derivatives have been investigated. LCMS, FT-IR, H NMR, and C NMR spectroscopy techniques were used to elucidate the structures of the synthesized compounds.

The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways.

Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants.

The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models.

Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymes.

In contemporary medicinal chemistry, employing a singular small molecule to concurrently multi-target disparate molecular entities is emerging as a potent strategy in the ongoing battle against metabolic disease. In this study, we present the meticulous design, synthesis, and comprehensive biological evaluation of a novel series of 1,2,3-triazolylmethylthio-1,3,4-oxadiazolylbenzenesulfonamide derivatives (8a-m) as potential multi-target inhibitors against human carbonic anhydrase (EC.4.