An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes

Bansal, Garima; Veeraveedu, Punniyakoti T.; Maurya, Rahul; Chawla, Pooja; Ramamurthy, Srinivasan

doi:10.1016/j.jare.2020.01.008

Cited by 66 publications

(44 citation statements)

References 94 publications

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“…The increase in HOMA-β associated with FOXO1 inhibitor treatment may be secondary to improvements in glycemia, and should be investigated in future studies. Interestingly, FOXO1 inhibition tended to reduce body weight and adiposity, in contrast to the weight gain associated with PPARγ agonists as well as insulin [ 20 , 21 ]. Furthermore, notwithstanding the theoretical liability that FOXO1 inhibition may activate lipogenesis and worsen dyslipidemia [ 10 ], compound 10 was neutral on hepatic steatosis and did not increase circulating triglycerides or cholesterol.…”

Section: Discussionmentioning

confidence: 99%

FOXO1 inhibition synergizes with FGF21 to normalize glucose control in diabetic mice

Lee

Diaz

Deroose

et al. 2021

Molecular Metabolism

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Objective Forkhead box protein O1 (FOXO1) plays a key role in regulating hepatic glucose production, but investigations of FOXO1 inhibition as a potential therapeutic approach have been hampered by a lack of selective chemical inhibitors. By profiling structurally diverse FOXO1 inhibitors, the current study validates FOXO1 as a viable target for the treatment of diabetes. Methods Using reporter gene assays, hepatocyte gene expression studies, and in vivo studies in mice, we profiled our leading tool compound 10 and a previously characterized FOXO1 inhibitor, AS1842856 (AS). Results We show that AS has significant FOXO1-independent effects, as demonstrated by testing in FOXO1-deficient cell lines and animals, while compound 10 is highly selective for FOXO1 both in vitro and in vivo and fails to elicit any effect in genetic models of FOXO1 ablation. Chronic administration of compound 10 improved insulin sensitivity and glucose control in db/db mice without causing weight gain. Furthermore, chronic compound 10 treatment combined with FGF21 led to synergistic glucose lowering in lean, streptozotocin-induced diabetic mice. Conclusions We show that the widely used AS compound has substantial off-target activities and that compound 10 is a superior tool molecule for the investigation of FOXO1 function. In addition, we provide preclinical evidence that selective FOXO1 inhibition has potential therapeutic benefits for diabetes as a monotherapy or in combination with FGF21.

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Section: Discussionmentioning

confidence: 99%

FOXO1 inhibition synergizes with FGF21 to normalize glucose control in diabetic mice

Lee

Diaz

Deroose

et al. 2021

Molecular Metabolism

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“…Detection was done under ultraviolet light at 254 nm. 1 H NMR (400 MHz), 13 C NMR (100 MHz) and 19 F NMR (376.5 MHz) spectra were recorded on a Bruker 400 MHz spectrometer using DMSO-d6 or CDCl3 as solvents and TMS at 0.00 ppm as an internal standard. Values for the chemical shifts are expressed in parts per million (ppm).…”

Section: Methodsmentioning

confidence: 99%

“…1,3-Thiazolidine-2,4-dione (TZD)-containing compounds have been reported to show many different pharmacological activities. 1 A few of these compounds are indicated in Figure 1. Glitazones, like rosiglitazone (1), are currently marketed for the treatment of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of some new 5-arylidene-2,4-thiazolidinedione esters

Tshiluka¹,

Bvumbi²,

Ramaite³

et al. 2021

Arkivoc

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Compounds containing the 1,3-thiazolidine-2,4-dione scaffold are gaining increasing scientific interest as potential interventional agents for a variety of disease states. A four-step synthesis of ethyl-(2-(5-arylidine-2,4dioxothiazolidin-3-yl)acetyl)glycinates, alaninates, butanoates, valinates and norvalinates is described. The synthesis began by converting 1,3-thiazolidine-2,4-dione into its potassium salt, which was treated with ethyl (2-chloroacetamido)glycinates, alaninates, butanoates, valinates and norvalinates, respectively, to obtain the penultimate products. These products were then subjected to a Knoevenagel condensation reaction with different aldehydes to obtain the desired products in low to excellent yields.

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“…Peroxisome proliferator-activated receptor gamma (PPARγagonists, rosiglitazone and pioglitazone, are drugs in clinical use for diabetes (61). Insulin resistance amplifies inflammation, associated with an increase in C-reactive protein, IL-6, and TNF-α (62) and produces a pro-coagulant state with increased fibrinogen and plasminogen activator inhibitor, (PAI-1) (63).…”

Section: Pparγ Agonistsmentioning

confidence: 99%

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs

Scala

Pacelli

2020

Front. Immunol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the "cytokine storm syndrome," a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered.

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An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes

Cited by 66 publications

References 94 publications

FOXO1 inhibition synergizes with FGF21 to normalize glucose control in diabetic mice

FOXO1 inhibition synergizes with FGF21 to normalize glucose control in diabetic mice

Synthesis of some new 5-arylidene-2,4-thiazolidinedione esters

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs

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