Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

Introduction: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models.

Methods: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively.

Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

Background: Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study.

Objectives: The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853.

Flavone-based novel antidiabetic and antidyslipidemic agents.

The hybrid congeners 62-90 of 6- and 7-hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice.

Dose escalation pharmacokinetics and lipid lowering activity of a novel farnesoid X receptor modulator: 16-Dehydropregnenolone.

Objectives: To study the dose escalation pharmacokinetics and lipid lowering activity of a novel FXR modulator, 16-Dehydropregnenolone (DHP).

Materials And Methods: The disposition of DHP following oral (36, 72, 100 and 150 mg/kg) and intravenous (1, 5 and 10 mg/kg) administration and its dose-response relationship were carried out in Sprague-Dawley rats. DHP and its metabolite 5-pregnene-3β-ol-16, 17-epoxy-20-one (M1) were analyzed by a validated LC-MS/MS method in plasma after intravenous and oral administration.

Synthesis and antidyslipidemic activity of chalcone fibrates.

A series of chalcone based PPAR-α agonists were synthesized and evaluated for their antidyslipidemic activity in high fructose high fat fed dyslipidemic Syrian golden hamsters. Most of the compounds exhibited antidyslipidemic activity. The compounds 4c and 4f have been identified as most potent antidyslipidemics.

In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats.

Objectives: The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity.

Methods: Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method.

Key Findings: The absorption rate constant was 0.

Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice.

Gugulipid, an ethyl acetate extract of the resin of plant Commiphora whighitii is an established hypolipidemic agent in clinical practice. The major constituent of gugulipid is guggulsterone [4, 17 (20)-pregnadiene-3, 16-dione]. It has been observed recently that patients receiving lipid-lowering drugs like statins have a reduced risk of dementia.

Chalcone based aryloxypropanolamines as potential antihyperglycemic agents.

A series of chalcone based aryloxypropanolamines were synthesized and evaluated for their antihyperglycemic activity in SLM and STZ rat models. Most of the compounds exhibited moderate to good activity ranging from 6.5% to 31.

Acyclic pyrazolo[3,4-d]pyrimidine nucleoside as potential leishmaniostatic agent.

A new synthesis of 6-amino-1-hydroxyethoxymethyl-4 (5H)-oxopyrazolo[3, 4-d]pyrimidine (4) has been mentioned. Compound 4 exhibited inhibition of amastigotes of Leishmania donovani to the extent of 89 % at 30 microg/mL, whereas iso-guanine analogue 5 had the inhibition only to the extent of 52.8% at 100 microg/mL in vitro.

Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines.

A series of aryloxypropanolamines (5a-r) of different chalcones (3a-e) were synthesized and evaluated for antihyperglycemic activity in sucrose loaded (SLM) and streptozotocin (STZ) induced diabetic animal models. Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SLM and STZ animal models.

Cardioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol induced myocardial ischemia in rats: A comparative study.

Guggulsterone, a mixture of cis (E) and trans (Z) isomers (7∶3 w/w) was synthesized from 16-DPA. The isomers were separated by column chromatography and evaluated for cardioprotective and antioxidant activities. Myocardial necrosis induced by isoproterenol in rats caused marked increase in serum creatine phosphokinase and glutamate pyruvate transaminase.