Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

Molecules, Год журнала: 2023, Номер 28(15), С. 5686 - 5686

Опубликована: Июль 27, 2023

Five-membered heteroaromatic rings, in particular, have gained prominence medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors developing effective drugs. The unique physicochemical properties biological effects of five-membered heterocycles positioned them key structural motifs numerous clinically Hence, the exploration five-ring remains an important research area chemistry, with aim discovering new therapeutic agents for various diseases. This review addresses incorporation heteroatoms such nitrogen, oxygen sulfur into aromatic ring these heterocyclic compounds, enhancing their polarity facilitating both stacking interactions formation hydrogen bonds. Histone deacetylases are present multiprotein complexes within epigenetic machinery play a central role cellular processes. They emerged targets cancer, neurodegenerative diseases other indications. In histone deacetylase inhibitors (HDACi's), perform functions zinc-binding group, linker or head contributing to binding activity selective recognition. focuses on providing up-to-date overview different utilized HDACi motifs, highlighting properties. It summarizes relevant publications from past decade, offering insights recent advancements this field research.

Язык: Английский

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Thiazolidinedione an auspicious scaffold as PPAR-γ agonist: its possible mechanism to Manoeuvre against insulin resistant diabetes mellitus

European Journal of Medicinal Chemistry Reports, Год журнала: 2024, Номер 11, С. 100160 - 100160

Опубликована: Апрель 21, 2024

Thiazolidinedione (TZD) plays a crucial role in activating PPAR-γ receptor, which helps to inhibit insulin-resistant Diabetes Mellitus through binding with DNA by forming complex retinoid receptors. TZD derivatives are the sulphur and nitrogen containing heterocyclic compounds that have massive impact synthetic chemistry for their plethora of pharmacological activities. improve insulin resistance lowering blood glucose level oxidation carbohydrate case type II Mellitus. scaffold is pentacyclic sulphur-containing compound two carbonyl groups an alpha hydrogen offering huge possibility structural modification this biologically active molecule, here N-3 & C-5 positions most versatile site nucleus. In review, we focus on brief description its antidiabetic activity mechanism action, structure relationship various approach main pharmacophore hope it will help develop idea about moiety future researchers.

Язык: Английский

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Design, synthesis, bioassay, and in silico studies of thiazolidinedione–morpholine hybrid ionic liquids as new antidiabetic agents

Journal of Molecular Liquids, Год журнала: 2025, Номер unknown, С. 127050 - 127050

Опубликована: Янв. 1, 2025

Язык: Английский

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Facile synthesis, antimicrobial activity, and molecular docking analysis of 8-hydroxyquinoline-4-thiazolidinone hybrids

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Фев. 14, 2025

8-Hydroxyquinoline and 4-thiazolidinone derivatives are promising antimicrobial agents, recognized for their activity against resistant pathogens. The aim of this study is to develop 8-hydroxyquinoline-4-thiazolidinone as potential agents. Using a one-pot reaction with sodium tetrafluoroborate an efficient eco-friendly catalyst, compounds 6a - l were synthesized subsequently screened antibacterial antifungal activity. Additionally, molecular docking dynamic simulations performed evaluate the active gain deeper insights into Compounds 6f 6 g showed superior ciprofloxacin, particularly Gram-negative bacteria, while 6b, g, h demonstrated strong effects. Molecular docking, dynamics simulations, MM-GBSA calculations highlighted binding interactions stable conformations within pocket FabZ enzyme. ADMET analyses further indicated that these possess favorable drug-like properties. hybrids exhibit broad-spectrum agents merit investigation drug candidates.

Язык: Английский

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Innovative Multitarget Organoselenium Hybrids With Apoptotic and Anti‐Inflammatory Properties Acting as JAK1/STAT3 Suppressors

Drug Development Research, Год журнала: 2025, Номер 86(2)

Опубликована: Март 18, 2025

ABSTRACT Herein, we report the design, synthesis, and characterization of novel organoselenium (OSe) hybrids ( 5 – 19 ) via modifications lead, N ‐(4‐selaneylphenyl)‐2‐selaneylacetamide. The OSe‐based thiazol 9 showed highest growth inhibition % (GI%) 64.72% relative to positive reference doxorubicin (DOX), with a GI% 79.5%. Furthermore, OSe derivatives low values compared normal cell lines employed, demonstrating their selectivity. tethered ‐chloroacetamide Schiff base cytotoxic effect an IC 50 (25.07 11.61 µM), respectively, against A549 tumor line (34.22 20.12 HELA cancer line. Enzyme‐linked immunosorbent assay study JAK1 STAT3 inhibitory potentials compounds in cells both promising activities 25.07 µM, respectively. Protein expression analysis on upregulation P53, BAX, Caspases 3, 6, 8, as apoptotic proteins. However, candidates expressed downregulation antiapoptotic proteins (BCL2, MMP2, MMP9). Moreover, described examined inflammatory proteins: COX2, IL‐6, IL‐1β. In addition, compound potential cycle arrest at G0, S, G2‐M layers, increase cellular levels. Finally, molecular docking studies most toward target receptors, binding scores interactions exceeding that cocrystallized inhibitor JAK1.

Язык: Английский

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Design, and synthesis of 2,4-thiazolidinedione substituted 1–3-5-triazine derivatives as anti-HIV agent via inhibition of reverse transcriptase along with anti-SARS CoV-2, antibacterial and antibiofilm activity

Bioorganic Chemistry, Год журнала: 2025, Номер 160, С. 108427 - 108427

Опубликована: Апрель 2, 2025

Язык: Английский

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Design and synthesis of a novel quinoline thiazolidinedione hybrid as a potential antidiabetic PPARγ modulator

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Июнь 1, 2025

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) remains a critical target for antidiabetic drug development due to its role in glucose and lipid metabolism. However, the adverse effects associated with full agonists of thiazolidinedione (TZD) class, such as weight gain hepatotoxicity, limit their clinical utility. Herein, we report design synthesis ( Z )-5-benzylidene-3-((2-chloroquinolin-3-yl)methyl)thiazolidine-2,4-dione (compound 7 ), novel TZD derivative that functions potential PPARγ modulator. Compound reduced blood level (BGL) by 22.33% after 15 days treatment daily single oral dose, demonstrating an effect comparable TZDs. Additionally, it elevated expression 75% activation induced Pioglitazone (PIO). Further characterization safety profile reveals compound is safer on liver compared PIO, alanine transaminase (ALT) aspartate (AST) levels remained significantly lower (147.4 ± 4.2 IU/L 229.9 2.7 IU/L, respectively). Moreover, exerts protective hepatic pancreatic tissues. Computational metabolic studies predict does not produce toxic metabolites or undergo hydrolysis ring, contributing improved safety. The docking into ligand-binding domain (LBD) demonstrates unique binding mode, positioning centrally within LBD interacting key amino acids selective modulation. These findings emphasize modulator dissociate insulin-sensitizing from side effects, offering alternative current TZD-based therapies.

Язык: Английский

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Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives

ACS Omega, Год журнала: 2023, Номер 9(1), С. 1810 - 1820

Опубликована: Дек. 28, 2023

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit formation advanced end products. In present work, we report synthesis characterization four 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1–4) compounds their human serum albumin inhibitory activity. One 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in initial, intermediary, final products reactions. Besides, conformational changes α-helix β-sheet (due hyperglycemia) were also found be reversed upon addition (3). Experimental findings complemented by computational [molecular docking, ADME/Tox, density functional theory (DFT)] studies. docking scores order 1 > 3 2 4, indicating importance polar group at moiety. results ADME/Tox DFT calculations revealed safe nature high drug-likeness stability. Overall, speculate that this study could provide valuable insights into biological activity 4-thiazolidinones.

Язык: Английский

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L‐proline‐based DES in Knoevenagel synthesis of arylidene rhodanines, thiazolidine‐2,4‐diones, and barbituric derivatives

Journal of Heterocyclic Chemistry, Год журнала: 2024, Номер 61(6), С. 1015 - 1023

Опубликована: Апрель 9, 2024

Abstract Deep eutectic solvents (DES) are environmentally friendly that prevent the use of toxic organic and have been extensively studied in recent years. However, volatile compounds (VOC) often still used during workup isolation products. Here, a zero‐VOC strategy for Knoevenagel reaction is reported. (Hetero)aromatic aldehydes successfully condensed with rhodanine, thiazolidine‐2,4‐dione TZD, or barbituric acid under mild conditions an L‐proline‐based DES pure obtained after hydrolysis without any purification. For less reactive activation by microwave allows diminution time from 24 h to just 1 h.

Язык: Английский

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The synthesis and antitumor activity of novel 1-alkyl-3-phenyland 3-alkyl-1-phenylimidazothiazolotriazines

Chemistry of Heterocyclic Compounds, Год журнала: 2024, Номер 60(3-4), С. 196 - 204

Опубликована: Апрель 1, 2024

Язык: Английский

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