Study of new interactions of glitazone’s stereoisomers and the endogenous ligand 15d-PGJ2 on six different PPAR gamma proteins

15-Deoxy-∆-12,14-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-γ: Function and Mechanism

“…The N-terminal functional region of PPAR- γ contains a phosphorylation site mitogen-activated protein kinase (MAPK). After 15d-PGJ2 enters cells and binds to PPAR- γ , activation results in the formation of heterodimers with retinoid X receptor alpha (RXR α ) and subsequent binding to specific DNA sequences to activate expression of target genes [8]. This specific DNA sequence, found in genes encoding hexanoyl coenzyme A synthase, lipoprotein lipase (LPL), insulin receptor substrate-2 (IRS-2), leptins, and tumour necrosis factor-alpha (TNF- α ), is known as the peroxisome proliferator response element (PPRE) [9].…”

A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin-Induced Rat Model of Diabetes

“…These receptors are found in diverse tissues. Through the activation of PPAR-γ, thiazolidinediones (TZDs, also known as glitazones) modify the transcription of genes that encode for factors involved in the intake of glucose (e.g., GLUT-4 [5,6]) and in the metabolism of glucose and fatty acids [4,7]. Accordingly, they promote the sensitization of tissues to insulin.…”

“…Regarding TZDs that serve as PPAR-γ agonists (Figure 1), the structure contains an acid region (a TZD ring acting as the pharmacophore), an aromatic center, and a cyclic polar/nonpolar region or hydrophobic side chain [5][6][7][8][9][10]. Due to the relatively large ligandbinding pocket (1200 Å 3 ) of the receptor [4,7], numerous chemical modifications have been proposed to construct glitazone derivatives, generating great structural diversity [5][6][7][8][9][10]. Several authors have suggested that the presence of a double bond in carbon 5 of glitazone derivatives is a favorable characteristic [5][6][7][8]11].…”

“…Due to the relatively large ligandbinding pocket (1200 Å 3 ) of the receptor [4,7], numerous chemical modifications have been proposed to construct glitazone derivatives, generating great structural diversity [5][6][7][8][9][10]. Several authors have suggested that the presence of a double bond in carbon 5 of glitazone derivatives is a favorable characteristic [5][6][7][8]11]. The resulting unsaturated tail prevents racemization and provides rigidity to the molecule [7], possibly explaining the capacity of such glitazone derivatives to increase PPAR-γ expression in vitro and in vivo (in rat models of type 2 diabetes), and thus to decrease hyperglycemia [5,6,8].…”

“…Several authors have suggested that the presence of a double bond in carbon 5 of glitazone derivatives is a favorable characteristic [5][6][7][8]11]. The resulting unsaturated tail prevents racemization and provides rigidity to the molecule [7], possibly explaining the capacity of such glitazone derivatives to increase PPAR-γ expression in vitro and in vivo (in rat models of type 2 diabetes), and thus to decrease hyperglycemia [5,6,8].…”