Dual PPAR-α and -γ activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential

Madhavan, Gurram R.; Chakrabarti, Ranjan; Reddy, K. Anantha; Rajesh, B. M.; Balraju, V.; Rao, Praveen; Rajagopalan, Rukkumani; Iqbal, Javed

doi:10.1016/j.bmc.2005.08.043

Cited by 66 publications

(18 citation statements)

References 11 publications

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“…PPAR-α and PPAR-γ activators have been demonstrated to exert cardiovascular protective effects independent of their metabolic actions [58]. However, recent studies with dual PPAR activators have cast doubts on their clinical efficacy in cardiovascular prevention compared with the original PPAR activators currently marketed [59, 60]. …”

Section: Etiologymentioning

confidence: 99%

Diabetes and Hypertension: Is There a Common Metabolic Pathway?

Cheung

2012

Curr Atheroscler Rep

465

325

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Diabetes and hypertension frequently occur together. There is substantial overlap between diabetes and hypertension in etiology and disease mechanisms. Obesity, inflammation, oxidative stress, and insulin resistance are thought to be the common pathways. Recent advances in the understanding of these pathways have provided new insights and perspectives. Physical activity plays an important protective role in the two diseases. Knowing the common causes and disease mechanisms allows a more effective and proactive approach in their prevention and treatment.

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Section: Etiologymentioning

confidence: 99%

Diabetes and Hypertension: Is There a Common Metabolic Pathway?

Cheung

2012

Curr Atheroscler Rep

465

325

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“…Molecules with bulky moiety like benzoxazine attached through an optimum size linker of three atoms to the classical L1 and thiazolidinedione ring would result dual agonistic activity with a potential of a drug lacking side effects [111]. …”

Section: Structure Activity Relationship Studies On Thiazolidinedimentioning

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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“…TZDs are a class of insulin sensitizing drugs, which include ciglitazone, pioglitazone, troglitazone and rosiglitazone [15]. TZDs are known to stimulate PPAR-γ receptor, they also have multiple PPAR-γ independent biological profiles, such as antimalarial [16], antioxidant [17], antitumor [18], cytotoxic [19], anti-inflammatory [20], antimicrobial [21], radical scavenger [22], glycogen synthase kinase (GSK) 3 inhibitor [23], chymase inhibitor [24], aldose reductase inhibitor [25], cholesterol esterase inhibitor [26], thyroid hormone receptor antagonist [27] and neuroprotective [28].…”

Section: Methodsmentioning

confidence: 99%