Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists

Darwish, Khaled M.; Salama, Ismail; Mostafa, Samia M.; Gomaa, Mohamed S.; Helal, Mohamed A.

doi:10.1016/j.ejmech.2015.12.049

Cited by 65 publications

(35 citation statements)

References 55 publications

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“…Therapies targeting insulin resistance to improve asthma control may benefit obese asthmatic adults with insulin resistance. Traditional insulin sensitisers [36], such as biguanides (like metformin) and thiazolidinediones (like pioglitazone), or emerging ones (such as free fatty acid receptor 1 agonists [37] or BGP-15 [38]), could be preferentially used in obese, insulin-resistant, asthmatic adults allowing a precision medicine approach. Additionally, it is possible that some of these drugs, metformin for example, which is now used for weight loss in nondiabetics with obesity, may have some benefit in obese asthmatics without diabetes.…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance modifies the association between obesity and current asthma in adults

et al. 2016

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Insulin resistance potentiates the association between obesity and childhood asthma, but this relationship appears inconsistent in relatively small studies of adults. We investigated effect modification in adults using the National Health and Nutrition Examination Survey 2003–2012, a large, nationally representative database. Insulin resistance and a history of physician-diagnosed current asthma were obtained from 12 421 adults, ages 18–85 years. We used logistic regression to determine associations between obesity and current asthma, adjusting for age, sex, race/ethnicity, poverty income ratio and smoking status. An interaction term evaluated effect modification by insulin resistance of the obesity–asthma association. As expected, obesity was positively associated with current asthma. Insulin resistance modified this association, with obesity measured as body mass index, waist circumference or waist-to-height ratio. The relationship between obesity and current asthma was stronger with increasing insulin resistance tertiles (OR 2.05, 95% CI 2.76–3.00; p-value for interaction 0.03). This association was robust to adjustments for other components of the metabolic syndrome (hypertriglyceridaemia, hypertension, hyperglycaemia and systemic inflammation). None of these components were themselves effect modifiers of the obesity–asthma association. In this large, nationally representative sample, insulin resistance modified the association between obesity and current asthma in adults. Targeting insulin resistance may represent a novel therapeutic strategy for obese patients with asthma.

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Section: Discussionmentioning

confidence: 99%

Insulin resistance modifies the association between obesity and current asthma in adults

et al. 2016

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“…These derivatives possess the classical topology of the synthetic agonists and the lipophilic tail consists of bulky groups like biphenyl and benzimidazole [127]. …”

Section: Free Fatty Acid Receptor 1 (Ffar1) As Emerging Target Formentioning

confidence: 99%

Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs

Thangavel

Bratty

Javed

et al. 2017

International Journal of Medicinal Chemistry

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Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.

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“…Darwish i wsp. [39] opisali dziewięć związków, które wśród 19 badanych wykazywały zadawalające oczekiwane efekty farmakologiczne, a dwa z nich (z podstawnikami benzimidazolowymi oraz bifenylowymi) cechowały się najbardziej pożądanymi wartościami powinowactwa receptorowego do obydwu typów PPAR-γ/FFAR1 w zakresie niskich stężeń i zostały skierowane do dalszych etapów badań przedklinicznych.…”

Section: Prace Nad Nowymi Lekami Wykorzystującymi Mechanizm Agonistycunclassified

Agoniści receptorów aktywowanych proliferatorami eroksysomów w farmakoterapii. Obecne znaczenie i perspektywy zastosowania

Dobrek¹

2017

PiS

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Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists

Cited by 65 publications

References 55 publications

Insulin resistance modifies the association between obesity and current asthma in adults

Insulin resistance modifies the association between obesity and current asthma in adults

Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs

Agoniści receptorów aktywowanych proliferatorami eroksysomów w farmakoterapii. Obecne znaczenie i perspektywy zastosowania

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