Modulation of PPAR subtype selectivity. Part 2: Transforming PPARα/γ dual agonist into α selective PPAR agonist through bioisosteric modification

Zaware, Pandurang; Shah, Shailesh R.; Pingali, Harikishore; Makadia, Panlcaj; Thube, Baban; Pola, Suresh; Patel, Darshit; Priyadarshini, Priyanka; Suthar, Dinesh; Shah, Maanan; Jamili, Jeevankumar; Sairam, Kalapatapu V.V.M.; Giri, Suresh; Patel, Lala; Patel, Harilal; Sudani, Hareshkumar; Patel, Hiren; Jain, Mukul; Patel, Pankaj; Bahekar, Rajesh

doi:10.1016/j.bmcl.2010.12.032

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…Among these targets, TZDs or glitazones 4 are synthetic, high-affinity ligands of peroxisome proliferator activated receptor-gamma (PPARγ) 5 . Of the thiazolidine-2, 4-dione compounds 6,7 , pioglitazone and rosiglitazone are selective PPARγ agonists 8 . Further comparative studies of both glitazones, rosiglitazone is associated with a significantly increased the risk of myocardial infarction, heart failure and death as a result of cardiovascular complication 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Docking Studies and Biological Evaluation of 5-[4-(Substituted) Benzylidene or Benzyl] Thiazolidine-2, 4-Dione With Their Oral Hypoglycemic Activity

Roy¹,

Dumbare²,

Harak³

et al. 2013

Int. Res. J. Pharm.

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A new series of 5-[4-(substituted) benzylidene or benzyl] thiazolidine-2, 4-dione (TZDs) have been synthesized using economical synthetic routes. The aim of the synthesis based on modification of linker region and effector region of rosiglitazone. Among these newly synthesized compounds, based on their docking results, some compounds were selected for study of oral hypoglycemic activity on fructose induced hyperglycemia in Wistar rats. The results of selected compounds shows that, 5-[4-(2-amino-5-ethoxypyridine) sulphonyl benzylidene] thiazolidine-2, 4-dione and 5-[4-(2-amino-5-ethoxypyridine) ethoxy benzyl] thiazolidine-2, 4-dione have appreciable blood glucose-lowering effect compared to that of the reference drug, pioglitazone. Out of these two compounds, 5-[4-(2-amino-5-ethoxypyridine)ethoxy benzyl] thiazolidine-2, 4-dione shows better hydrogen bond interaction with amino acid residues of peroxisome proliferator activated receptor-gamma (PPARγ) and also shows better oral hypoglycemic activity in this series

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Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Docking Studies and Biological Evaluation of 5-[4-(Substituted) Benzylidene or Benzyl] Thiazolidine-2, 4-Dione With Their Oral Hypoglycemic Activity

Roy¹,

Dumbare²,

Harak³

et al. 2013

Int. Res. J. Pharm.

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“…Then we turned to another well-known method of alkylation of oximes, specifically, reaction with dibromoalkanes [16,17]. An analog of steviolbioside oxime V, oxime XI with a protected carboxy group, was used.…”

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confidence: 99%

Functionalization of the double bond in the glycoside of the Stevia rebaudiana plant steviolbioside, as a way to macrocyclic glycosides

et al. 2015

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The С 16 =С 17 bond in the glycoside steviolbioside from the plant Stevia rebaudiana was oxidized for the first time. Ketone, thiosemicarbazone, and oxime of steviolbioside with a heptaacetylated sophorosyl fragment, as well as binuclear and tetranuclear macrocyclic derivatives of this rebaudioside were synthesized.The 1 Н NMR spectra of glycosides I-VI show characteristic signals of the С 20 Н 3 (0.99-1.23 ppm) and С 18 Н 3 protons (1.24-1.34 ppm), as well as the С 14 Н α proton as doublet at 2.70 ppm in stevioside I and as doublet of doublets at 2.46-2.56 ppm in glicosides II, IV. The anomeric protons of the sophorosyl fragment

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“…Although it is possible that orally administered ZYM-201 sodium succinate can be converted into a metabolite with direct antioxidative properties, these data suggest a role as an indirect modulator that enhances cellular antioxidative enzyme systems. Reports that the PPAR response element is located in the promoter region of the SOD gene [31], that PPARα agonists show antihyperlipidemic effects [35], and that saponin fractions functionally regulate the role of PPAR [30], also led us to assume the possibility that ZYM-201 sodium succinate can act as a modulator of the PPAR-mediated regulatory pathway. This hypothesis will be explored in detail in a future study.…”

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confidence: 99%

ZYM-201 Sodium Succinate Ameliorates Streptozotocin-Induced Hyperlipidemic Conditions

et al. 2011

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ZYM-201 is a methyl ester of a novel triterpenoid glycoside. It is isolated from SANGUISORBA OFFICINALIS, a widely used medicinal plant in Korea, China, and Japan, that is prescribed for various diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. In this study, the antihyperlipidemic effect of the salt form (sodium succinate) of ZYM-201 was examined using streptozotocin (STZ)-treated hyperglycemic rats. Oral administration of ZYM-201 sodium succinate (3 to 10 mg/kg) resulted in recovery of the increased serum levels of triglyceride (TG) and total cholesterol (TC) back to normal levels. Elevated levels of serum lipoproteins, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), were also significantly restored by this compound without altering 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. Finally, ZYM-201 sodium succinate displayed antioxidative properties, including suppression of lipid peroxide and hydroxyl radical generation and upregulation of superoxide dismutase (SOD) activity. Therefore, our data strongly suggest that ZYM-201 sodium succinate can be used as a remedy for the treatment of diabetes-derived hyperlipidemic disorders such as atherosclerosis and vascular diseases.

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Modulation of PPAR subtype selectivity. Part 2: Transforming PPARα/γ dual agonist into α selective PPAR agonist through bioisosteric modification

Cited by 9 publications

References 30 publications

Synthesis, Molecular Docking Studies and Biological Evaluation of 5-[4-(Substituted) Benzylidene or Benzyl] Thiazolidine-2, 4-Dione With Their Oral Hypoglycemic Activity

Synthesis, Molecular Docking Studies and Biological Evaluation of 5-[4-(Substituted) Benzylidene or Benzyl] Thiazolidine-2, 4-Dione With Their Oral Hypoglycemic Activity

Functionalization of the double bond in the glycoside of the Stevia rebaudiana plant steviolbioside, as a way to macrocyclic glycosides

ZYM-201 Sodium Succinate Ameliorates Streptozotocin-Induced Hyperlipidemic Conditions

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