Revisiting glitazars: Thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents

Raval, Preeti; Jain, Mukul; Goswami, Amitgiri; Basu, Sujay; Gite, Archana; Godha, Atul K.; Pingali, Harikishore; Raval, Saurin; Giri, Suresh; Suthar, Dinesh; Shah, Maanan; Patel, Pankaj

doi:10.1016/j.bmcl.2011.03.020

Cited by 21 publications

(7 citation statements)

References 31 publications

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“…Hydrocinnamate is a phenolic compound with well‐characterized antioxidant activity . Moreover, derivatives of this compound are known to have agonistic effects on peroxisome proliferator‐activated receptors with antidiabetic and lipid‐lowering activity .…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling of Long‐Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain

Menni

Migaud

Kastenmüller

et al. 2017

Obesity

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ObjectiveTo investigate the association between long‐term weight change and blood metabolites.MethodsChange in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3‐79.6, baseline BMI: 25.11 ± 4.35) measured for 280 metabolites at follow‐up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n = 1,760; age range: 25‐70, baseline BMI: 27.72 ± 4.53). The study examined whether the metabolites identified could prospectively predict weight change in KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n = 471; age range: 55‐74, baseline BMI: 27.24 ± 5.37).ResultsThirty metabolites were significantly associated with change in BMI per year in TwinsUK using Bonferroni correction. Four were independently associated with weight change in the multivariable LASSO model and replicated in KORA: namely, urate (meta‐analysis β [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 × 10−19), gamma‐glutamyl valine (β [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 × 10−20), butyrylcarnitine (β [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 × 10−12), and 3‐phenylpropionate (β [95% CI] = −0.03 [−0.041 to −0.019]; P = 9.8 × 10−8), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO.ConclusionsMetabolites linked to higher oxidative stress are associated with increased long‐term weight gain.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling of Long‐Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain

Menni

Migaud

Kastenmüller

et al. 2017

Obesity

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“…Many compounds, mainly dual- or pan-PPAR agonists, have been tested in the past decade to lower the adverse effect of a single agonist to PPARs. For example, a sequence of pharmaceutical molecules showing the dual effects of PPARα/γ agonists, called “glitazars”, has been studied for T2DM therapy [149]. However, most of these drugs were discontinued after clinical trials due to the variety of adverse effects associated with them [143].…”

Section: Discussionmentioning

confidence: 99%

PPARs as Nuclear Receptors for Nutrient and Energy Metabolism

et al. 2019

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It has been more than 36 years since peroxisome proliferator-activated receptors (PPARs) were first recognized as enhancers of peroxisome proliferation. Consequently, many studies in different fields have illustrated that PPARs are nuclear receptors that participate in nutrient and energy metabolism and regulate cellular and whole-body energy homeostasis during lipid and carbohydrate metabolism, cell growth, cancer development, and so on. With increasing challenges to human health, PPARs have attracted much attention for their ability to ameliorate metabolic syndromes. In our previous studies, we found that the complex functions of PPARs may be used as future targets in obesity and atherosclerosis treatments. Here, we review three types of PPARs that play overlapping but distinct roles in nutrient and energy metabolism during different metabolic states and in different organs. Furthermore, research has emerged showing that PPARs also play many other roles in inflammation, central nervous system-related diseases, and cancer. Increasingly, drug development has been based on the use of several selective PPARs as modulators to diminish the adverse effects of the PPAR agonists previously used in clinical practice. In conclusion, the complex roles of PPARs in metabolic networks keep these factors in the forefront of research because it is hoped that they will have potential therapeutic effects in future applications.

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“…Peroxisome proliferator-activated receptors (PPARs) play a very important role in metabolic syndrome whose major manifestations are hyperglycemia, dyslipidemia and obesity. Compound 100 was found to be the most efficacious PPAR α/γ dual agonist and showed the glucose reduction of 72% [60].…”

Section: Biological Activities Of Oxazolementioning

confidence: 99%

A comprehensive review on biological activities of oxazole derivatives

2019

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The utility of oxazole as intermediates for the synthesis of new chemical entities in medicinal chemistry have been increased in the past few years. Oxazole is an important heterocyclic nucleus having a wide spectrum of biological activities which drew the attention of researchers round the globe to synthesize various oxazole derivatives and screen them for their various biological activities. The present review article aims to review the work reported on therapeutic potentials of oxazole scaffolds which are valuable for medical applications during new millennium.

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Revisiting glitazars: Thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents

Cited by 21 publications

References 31 publications

Metabolomic Profiling of Long‐Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain

Metabolomic Profiling of Long‐Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain

PPARs as Nuclear Receptors for Nutrient and Energy Metabolism

A comprehensive review on biological activities of oxazole derivatives

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