ABSTRACT
The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.
Subject(s)
Chromones/therapeutic use , Dyslipidemias/drug therapy , Lipid Metabolism/drug effects , Piperidines/therapeutic use , Animals , Antioxidants , Chromones/pharmacology , Male , Piperidines/pharmacology , RatsABSTRACT
BACKGROUND: Flacourtia indica (Burm. f.) Merr. is a medicinal plant indigenous to India and is broadly used worldwide for the treatment of a variety of health ailments. The present study was experimented on hyperlipidemic Charles Foster rats with the aim to explore the possible mechanism responsible for the antidyslipidemic activity of the hydromethanolic extract from F. indica leaves (FIL). METHODS: Hyperlipidemia was induced by a single intraperitoneal dose of Triton WR-1339 in Charles Foster rats. The plasma lipid levels were estimated in control and treated groups. The antioxidant potential of F. indica was assessed in both enzymatic and non-enzymatic systems. An acute toxicity study of high-performance liquid chromatography (HPLC)-fingerprinted extract was carried out in Swiss albino mice. RESULTS: The F. indica extract at a dose of 150 mg/kg significantly lowers the plasma level of total cholesterol (17%), triglycerides (13%), and phospholipids (16%) by increasing post-heparin lipolytic activity (19%) and lecithin-cholesterol-acyltransferase activity (20%) in Triton-induced hyperlipidemic rats. In addition, the F. indica extract showed significant in vitro antioxidant and anti-adipogenic activity. HPLC analysis indicates the presence of flavanones and flavones in the extract, and the extract was found to be non-toxic up to a dose of 2000 mg/kg body weight in the acute oral toxicity study. CONCLUSIONS: These finding suggest that F. indica holds significant potential in preventing clinical deterioration induced by dyslipidemia along with oxidative stress.
Subject(s)
Dyslipidemias/drug therapy , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Salicaceae/chemistry , Animals , Antioxidants/metabolism , Cholesterol/blood , Disease Models, Animal , Dyslipidemias/blood , Flavanones/pharmacology , Flavones/pharmacology , Hypoglycemic Agents/pharmacology , Male , Mice , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Rats , Triglycerides/bloodABSTRACT
A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results suggest that these new hybrid architectures may serve as promising leads for the development of next generation lipid lowering agents.
Subject(s)
Antioxidants/pharmacology , Chalcone/pharmacology , Drug Design , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Indoles/pharmacology , Animals , Antioxidants/chemical synthesis , Antioxidants/chemistry , Chalcone/chemistry , Disease Models, Animal , Hyperlipidemias/chemically induced , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/chemistry , Indoles/chemistry , Lipoproteins/blood , Lipoproteins, HDL/blood , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/blood , Lipoproteins, LDL/metabolism , Male , Molecular Structure , Polyethylene Glycols/administration & dosage , RatsABSTRACT
As a part of our drug discovery program, we identified an alkaloidal amide i.e. Aegeline (V) isolated from the leaves of Aegle marmelos as a dual acting agent (antihyperlipidemic and antihyperglycemic). In continuation of this program, we synthesized new N-acyl-1-amino-2-alcohols (N-acrylated-1-amino-2-phenylethanol and N-acylated-1-amino-3-aryloxypropanols) via Ritter reaction and screened for their in-vivo antihyperlipdemic activity in Triton induced hyperlipidemia model, LDL-oxidation and antioxidant activity. Compounds 3, 11 and 13 showed good antihyperlipidemic activity, LDL-oxidation as well as antioxidant activity and comparable activity with marketed antidyslipidemic drug.
Subject(s)
1-Propanol/chemical synthesis , 1-Propanol/pharmacology , Drug Design , Lipoproteins, LDL/metabolism , Phenylethyl Alcohol/chemical synthesis , Phenylethyl Alcohol/pharmacology , 1-Propanol/chemistry , 1-Propanol/therapeutic use , Aegle/chemistry , Animals , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Lipoprotein Lipase/metabolism , Lipoproteins, LDL/blood , Liver/drug effects , Liver/enzymology , Male , Oxidation-Reduction/drug effects , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/therapeutic use , Plant Leaves/chemistry , Polyethylene Glycols/adverse effects , RatsABSTRACT
The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-ß-D-glucopyranoside and emodin 8-O-ß-D-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.
Subject(s)
Anthraquinones/pharmacology , Antioxidants/pharmacology , Dyslipidemias/drug therapy , Rheum/chemistry , Animals , Anthraquinones/chemistry , Anthraquinones/therapeutic use , Antioxidants/chemistry , Antioxidants/therapeutic use , Dyslipidemias/blood , Dyslipidemias/chemically induced , Emodin/pharmacology , Lipid Metabolism/drug effects , Lipids/blood , Liver/metabolism , Male , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Polyethylene Glycols , Rats , Rhizome/chemistryABSTRACT
Andrographis paniculata, native to Taiwan, Mainland China and India, is a medicinal herb, which possesses various biological activities including anti-atherosclerosis. Andrographolide (1) has been identified as one of the active constituents against atherosclerosis. In continuation of our drug discovery program we synthesized few novel derivatives of 1 to improve their antidyslipidemic, LDL-oxidation and antioxidant activity. The tosylated derivative 7 has been turned out to be more potent than the parent compound and comparable activity with marketed antidyslipidemic drugs.
Subject(s)
Antioxidants/pharmacology , Diterpenes/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Lipoproteins, LDL/metabolism , Animals , Antioxidants/administration & dosage , Antioxidants/chemical synthesis , Disease Models, Animal , Diterpenes/administration & dosage , Diterpenes/chemical synthesis , Humans , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/chemical synthesis , Lipoproteins, LDL/blood , Lipoproteins, LDL/chemistry , Male , Molecular Structure , Oxidation-Reduction , Rats , Rats, Inbred StrainsABSTRACT
In continuation of our drug discovery programme on Indian medicinal plants, we isolated an unusual amino acid, i.e. 2-amino-5-hydroxyhexanoic acid (1) from the seeds of Crotalaria juncea. The 2-amino-5-hydroxyhexanoic acid (1) showed dose dependent lipid lowering activity in the in vivo experiments and also showed good in vitro antioxidant activity. The cyclized compound, 3-amino-6-methyltetrahydro-2H-pyran-2-one (2) showed better lipid lowering and antioxidant profile than the parent compound 1.
Subject(s)
Antioxidants/therapeutic use , Caproates/therapeutic use , Crotalaria/chemistry , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Lipids/blood , Plant Extracts/therapeutic use , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Caproates/isolation & purification , Caproates/pharmacology , Dose-Response Relationship, Drug , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hypolipidemic Agents/isolation & purification , Hypolipidemic Agents/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Seeds/chemistryABSTRACT
A series of different benzofuran-bisindole hybrids were synthesized and evaluated in vitro for their antioxidant and in vivo for antidyslipidemic activity in triton WR-1339 induced hyperlipidemic rats. Among the series, compounds 4a, 4c, 4h and 4j showed significant decrease in plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) followed by increase in post heparin lipolytic activity (PHLA). In addition, the active hybrids possessed moderate antioxidant properties and increased the plasma lecithin cholesterol acyltransferase (LCAT) activity, which plays a key role in lipoprotein metabolism contributing to an increased level of HDL-C in serum. These results indicate that these hybrids constitute novel prototypes for the management of dyslipidemia.
Subject(s)
Antioxidants/pharmacology , Benzofurans/chemical synthesis , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/pharmacology , Indoles/chemical synthesis , Animals , Antioxidants/chemical synthesis , Antioxidants/chemistry , Benzofurans/chemistry , Benzofurans/pharmacology , Cholesterol/blood , Enzyme Activation/drug effects , Hypolipidemic Agents/chemistry , Indoles/chemistry , Indoles/pharmacology , Lipolysis/drug effects , Male , Molecular Structure , Phosphatidylcholine-Sterol O-Acyltransferase/blood , Phospholipids/blood , Rats , Triglycerides/bloodABSTRACT
A series of Lupeol-based chalcones have been synthesized aiming to enhance the therapeutic efficacy of parent compound, the novel compounds were evaluated for their antidyslipidemic activity in triton-WR 1339 induced hyperlipidemic rats. Among the ten synthesized chalcones, the most active K4, K8, and K9 reversed the plasma levels of TC by (24, 25, 27 %), phospholipid by (25, 26, 25 %) and triacylglycerol by (27, 24, 24 %) respectively. In addition, the compounds showed significant in vitro antioxidant activity. The lipid lowering activity of these compounds were mediated through lipoprotein lipase activation (12-21 %) and enhanced post-heparin lipolytic activity (15-16 %). The compounds also displayed noteworthy inhibitory effect on 3-hydroxy-3-methyl-glutaryl reductase activity (in vitro). The in vitro effect of the most active compounds on MDI-induced adipogenesis using 3T3-L1 preadipocytes at 10 and 20 µM concentrations showed significant inhibition (20-32 %) of adipogenesis.
Subject(s)
Adipocytes/drug effects , Antioxidants/pharmacology , Chalcones/pharmacology , Lipids/blood , Pentacyclic Triterpenes/chemistry , Animals , Antioxidants/isolation & purification , Cell Line , Chalcones/isolation & purification , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Hyperlipidemias/drug therapy , Lipid Peroxidation/drug effects , Male , Molecular Structure , Plant Bark/chemistry , RatsABSTRACT
In our continuing search for safe and efficacious antidyslipidemic agents, structurally interesting coumarin-chalcone fibrates were synthesized and evaluated in triton WR-1339 induced hyperlipidemic rats. The most active compound 41 decreased the total cholesterol (TC), phospholipids (PL) and triglycerides (TG), of hyperlipidemic rats by 26, 24, and 25% respectively. In addition, the compound 41 significantly reversed the levels of VLDL, LDL HDL and also increased the LPL activity. Altogether, our data suggests that these novel hybrids would be a potential new class of therapeutic agents against dyslipidemia.
Subject(s)
Chalcones/pharmacology , Coumarins/pharmacology , Dyslipidemias/drug therapy , Animals , Chalcones/chemistry , Coumarins/chemistry , Dyslipidemias/chemically induced , Male , Molecular Structure , Polyethylene Glycols , Rats , Rats, Inbred StrainsABSTRACT
: Alcoholic extract of Trigonella foenum graecum seeds [fenugreek seed extract (FSE)] was studied in triton-induced and high-fat diet-induced hyperlipidemia to evaluate antidyslipidemic effect. Plasma cholesterol (26.19%) and triglycerides (36.6%) were found to be lowered by FSE maximum at a dose of 200 mg/kg body weight in triton-treated hyperlipidemic rats. Chronic feeding of FSE (200 mg/kg body weight) caused lowering in plasma and hepatic lipid levels by activating lecithin-cholesterol acyltransferase (47%), postheparin lipolytic activity (35%), triglyceride lipase (34%), lipoprotein lipase (20.8%), and increased excretion of fecal bile acids (36%-45%). The FSE shows potent antioxidant activity in both in vitro and in vivo systems. It inhibited generation of superoxide anion and hydroxyl free radicals in both enzymatic and nonenzymatic systems significantly at 200 µM concentration. Furthermore, FSE normalizes the activities of antioxidant enzymes, that is, superoxide dismutase and catalase, and reduces plasma lipid peroxidation (33.9%), hepatic 4-hydroxynonenal (27%), and isoprostanes (28%). Data of the present study demonstrated that the T. foenum graecum seed extract has both antidyslipidemic and antioxidant properties.
Subject(s)
Antioxidants/pharmacology , Dyslipidemias/prevention & control , Hyperlipidemias/prevention & control , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Trigonella/chemistry , Animals , Bile Acids and Salts/metabolism , Cholesterol/blood , Disease Models, Animal , In Vitro Techniques , Lipoprotein Lipase/metabolism , Male , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Rats , Seeds/chemistry , Treatment Outcome , Triglycerides/bloodABSTRACT
Miglitol, an anti-diabetic drug, has been shown to reduce plasma lipids and inhibit free radical generation. The anti-hyperlipidemic and antioxidant effects of miglitol were studied in triton-induced hyperlipidemic rats and high fat diet-fed obese rats. Plasma cholesterol and triglycerides levels were significantly lowered by miglitol at 100 mg/kg body weight doses. Miglitol inhibited generation of superoxide anion and hydroxyl free radicals by 14 and 31 % in enzymatic systems and 19 and 25 % in non-enzymatic systems, respectively. The in-vitro effect of the drug on adipogenesis using 3T3-L1 preadipocytes at 2-, 5- and 10-µM concentrations showed significant inhibition of adipogenesis (34.2 %) at 10-µM concentration. High fat diet-fed rat model was used to investigate anti-hyperlipidemic, anti-obesity and antioxidant effect of miglitol. Miglitol increased the activities of lecithin-cholesterol-acyltransferase (19 %), post heparin lipolytic activity (26 %), lipoprotein lipase (26 %) and triglyceride lipase (31 %) which result in a decrease in plasma lipid levels. The antioxidant enzymes viz., catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and thioredoxin reductase were increased by the drug in the treated animals. The antihyperlipidemic and antioxidant effect of miglitol can be correlated to its effect on different enzymes and it can be used for inhibiting the development of cardiovascular diseases.
Subject(s)
1-Deoxynojirimycin/analogs & derivatives , Antioxidants/therapeutic use , Hyperlipidemias/drug therapy , Hypoglycemic Agents/therapeutic use , Obesity/drug therapy , 1-Deoxynojirimycin/pharmacology , 1-Deoxynojirimycin/therapeutic use , 3T3-L1 Cells , Adipogenesis/drug effects , Animals , Antioxidants/pharmacology , Body Weight/drug effects , Diet, High-Fat/adverse effects , Eating/drug effects , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hyperlipidemias/pathology , Hypoglycemic Agents/pharmacology , Lipids/analysis , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice , Obesity/blood , Obesity/etiology , Obesity/pathology , Polyethylene Glycols , RatsABSTRACT
A novel series of amide based fibrates were synthesized and evaluated for antidyslipidemic activity in triton induced hyperlipidemic rats. Interestingly, the compound 13 produced striking reduction in serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). In addition, it exhibited improved lipoprotein lipase activity and found to possess moderate radical scavenging potential. The results of the above studies shows that the compounds synthesized on fibrate based pharmacophores might result in identification of new lead for dyslipidemia.
Subject(s)
Amides/chemical synthesis , Antioxidants/chemical synthesis , Fibric Acids/chemical synthesis , Hyperlipidemias/drug therapy , Hypolipidemic Agents/chemical synthesis , Lipoprotein Lipase/blood , Amides/pharmacology , Animals , Antioxidants/pharmacology , Enzyme Activation/drug effects , Fibric Acids/pharmacology , Free Radicals/antagonists & inhibitors , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hyperlipidemias/enzymology , Hypolipidemic Agents/pharmacology , Lipid Peroxidation/drug effects , Male , Polyethylene Glycols , Rats , Structure-Activity RelationshipABSTRACT
Oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Excessively high levels of free radicals cause damage to cellular proteins, membrane lipids and nucleic acids, and eventually cell death. The present study was designed to investigate the possible effect of Azadirachta indica leaf extract in high fat diet induced diabetic Charles Foster rats. The increased level of lipidperoxidation and altered levels of enzymatic (superoxide dismutase, glutathione peroxidase and catalase) and non-enzymatic (glutathione) antioxidants were seen in high fructose fed animals. The treatment with A. indica leaf extract significantly normalized the altered levels of lipid peroxidation and antioxidant status at 400 mg/kg b.w. dose. The A. indica leaf extract was also tested for in vitro inhibition of generation of superoxide anion and hydroxyl free radical in both enzymatic and non-enzymatic systems. The A. indica leaf extract was found to inhibit generation of superoxide anion and hydroxyl free radical significantly at 200 µg/ml concentration. Data of present study demonstrated that the A. indica leaf extract has both antidiabetic and antioxidant properties.
Subject(s)
Antioxidants/administration & dosage , Azadirachta/chemistry , Diabetes Mellitus/drug therapy , Plant Extracts/administration & dosage , Animals , Diabetes Mellitus/metabolism , Diet, High-Fat/adverse effects , Disease Models, Animal , Humans , Lipid Peroxidation/drug effects , Male , Oxidative Stress/drug effects , RatsABSTRACT
Hypolipidemic and antiobesity effects of the newly synthesized indole-based fibrates were evaluated in Triton WR-1339 and high fat diet (HFD)-induced hyperlipidemic rats. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton model), in which compounds 3f and 3l showed significant antidyslipidemic activity. Furthermore, these compounds 3f and 3l were found to induce significant weight loss in the visceral fat mass of HFD-fed hyperlipidemic rats without affecting the normal feeding behavior. Histological examination of the liver of rats supplemented with 3f and 3l revealed a significant decrease in steatosis when compared to the effect of the standard drug fenofibrate. Additional effects such as an increase in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catabolism of I(131)-low density lipoproteins (LDL) confirm and reinforce the efficacy of both of these compounds as a new class of dual-acting hypolipidemic and antiobesity agents.
Subject(s)
Anti-Obesity Agents/chemical synthesis , Butyrates/chemical synthesis , Fibric Acids/chemical synthesis , Hypolipidemic Agents/chemical synthesis , Indoles/chemical synthesis , Propionates/chemical synthesis , Animals , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/pharmacology , Bile Acids and Salts/metabolism , Butyrates/chemistry , Butyrates/pharmacology , Dietary Fats , Fatty Liver/prevention & control , Feces/chemistry , Feeding Behavior/drug effects , Fibric Acids/chemistry , Fibric Acids/pharmacology , Hyperlipidemias/drug therapy , Hyperlipidemias/etiology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Indoles/chemistry , Indoles/pharmacology , Intra-Abdominal Fat/drug effects , Lipoproteins, LDL/blood , Liver/drug effects , Liver/pathology , Male , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Propionates/chemistry , Propionates/pharmacology , Rats , Structure-Activity Relationship , Weight Loss/drug effectsABSTRACT
An economical and efficient one-pot synthesis of a series of novel 5-aryl-6-cinnamoyl-7-methyl-flavanones has been developed by simple refluxing of cinnamoyl chalcones with NaOAc in aqueous ethanol in quantitative yields. These flavanones were screened for their in vitro antioxidant and in vivo antidyslipidemic activities. Among 24 compounds screened, four compounds 28, 29, 30, and 48 showed significant antidyslipidemic activities. However, out of all the compounds, only compound 28 exhibited significant antioxidant activity and other compounds showed moderate antioxidant activities.
Subject(s)
Antioxidants/chemical synthesis , Antioxidants/pharmacology , Flavanones/chemistry , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/pharmacology , Animals , Flavanones/chemical synthesis , Flavanones/pharmacology , Lipids/blood , Male , Molecular Structure , Rats , Structure-Activity RelationshipABSTRACT
A series of synthesized novel biscoumarin-chalcone hybrids were evaluated for their anti-inflammatory and antioxidant activity. The tested compounds significantly inhibit the carrageenin induced paw oedema in albino rats and also exhibit important scavenging activities. These compounds thus constitute an interesting template for the design of new therapeutic tools against inflammation.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Chalcone/chemistry , Coumarins/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Edema/drug therapy , Microsomes/metabolism , RatsABSTRACT
A series of novel benzocoumarin derivatives were synthesized and evaluated for their in vivo antidyslipidemic and in vitro antioxidant activities. Among 11 compounds tested, 2 compounds showed potent antidyslipidemic activity and 3 compounds showed potent antioxidant activity.
Subject(s)
Coumarins/therapeutic use , Dyslipidemias/drug therapy , Coumarins/chemistry , HumansABSTRACT
A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a-r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a-d (acid substituted) have shown significant glycogen phosphorylase activity.
Subject(s)
Dyslipidemias/drug therapy , Hypoglycemic Agents/chemical synthesis , Quinolines/chemical synthesis , Animals , Diabetes Mellitus, Experimental/drug therapy , Drug Design , Glycogen Phosphorylase/antagonists & inhibitors , Hypoglycemic Agents/pharmacology , Mice , Mice, Inbred Strains , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Quinolines/pharmacologyABSTRACT
A series of novel benzocoumarin derivatives were synthesized and evaluated for their in vivo anti-dyslipidemic and in vitro antioxidant activities. Preliminary screening indicates compound 4 as potential lead with significant lipid lowering and antioxidant activities. The study revealed that such attempts on benzocoumarin-based pharmacophores which is a biologically important scaffold might result in identification of new lead for anti-dyslipidemia.