Chemistry and Applications of Functionalized 2,4‐Thiazolidinediones

Ibrahim, Ayman; Shoman, Mai E.; Mohamed, Mamdouh F. A.; Hayallah, Alaa M.; Abuo‐Rahma, Gamal El‐Din A.

doi:10.1002/ejoc.202300184

Cited by 8 publications

(3 citation statements)

References 362 publications

(523 reference statements)

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“…Thiazolidinediones (TZDs) are mainly known for their role in type 2 diabetes, acting as PPARγ agonists thereby decreasing insulin resistance. Elucidation of side effects led to a decline in clinical use and a drop in research publications but the versatile nature of this scaffold promotes the application in many areas including anti-fungal, anti-bacterial and anti-cancer agents and as zinc binding groups [45,46].…”

Section: Thiazolidine-24-dionesmentioning

confidence: 99%

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

2023

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

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Section: Thiazolidine-24-dionesmentioning

confidence: 99%

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

2023

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“…One of the most studied modification in those scaffolds is the introduction of a benzylidene moiety on C5 via a Knoevenagel reaction [1,8]. Especially, in 2023, Ibrahim et al published a review on the chemistry and applications of functionalized thiazolidine-2,4-diones (TZD) in which they reported the different conditions used to perform Knoevenagel reaction on TZD [9]. Reactions are mainly performed in toluene, ethanol, or water and various catalysts can be used, the most common ones being amines and especially secondary amines.…”

Section: Introductionmentioning

confidence: 99%

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

Hesse,

Hertzog,

Rup‐Jacques

2024

Journal of Heterocyclic Chem

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

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“…Thiazolidin-4-one fits well into this criterion. 6,15 Despite the fact that thiazolidin-4-one-based compounds have been reported to inhibit the formation of AGEs, 16 limited research has been carried out. Intrigued by this, herein, we present the synthesis and characterization of four new 4-thiazolidinone derivatives (1−4) and the study of their human serum albumin (HSA) glycation inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

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

Haque,

Khan,

Alenezi

et al. 2023

ACS Omega

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

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Chemistry and Applications of Functionalized 2,4‐Thiazolidinediones

Cited by 8 publications

References 362 publications

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

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

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

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