The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ercin Erciyas - One of the best experts on this subject based on the ideXlab platform.
-
interaction of benzylidene hydrazono 1 4 dihydropyridines with β amyloid acetylcholine and Butyrylcholine esterases
2010Co-Authors: Vildan Alptuzun, Michaela Prinz, Verena Horr, Josef Scheiber, Krzysztof Radacki, Adyary Fallarero, Pia Vuorela, Bernd Engels, Holger Braunschweig, Ercin ErciyasAbstract:Abstract Approved drugs for the treatment of Alzheimer’s disease belong to the group of inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors. However none of the drugs is able to combat or reverse the progression of the disease. Thus, the recently reported promising multitarget-directed molecule approach was applied here. Using the lead compound DUO3, which was found to be a potent inhibitor of the AChE and Butyrylcholinesterase (BuChE) as well as an inhibitor of the formation of the amyloid (Aβ) plaque, new non-permanently positively charged derivatives were synthesized and biologically characterized. In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are appropriate to cross the blood–brain barrier due to their pKa values and lipophilicity, and to inhibit both the AChE and BuChE. More important some of the pyridinylidene hydrazones inhibit the Aβ fibril formation completely and destruct the already formed fibrils significantly.
-
interaction of benzylidene hydrazono 1 4 dihydropyridines with beta amyloid acetylcholine and Butyrylcholine esterases
2010Co-Authors: Vildan Alptuzun, Michaela Prinz, Verena Horr, Josef Scheiber, Krzysztof Radacki, Adyary Fallarero, Pia Vuorela, Bernd Engels, Holger Braunschweig, Ercin ErciyasAbstract:Approved drugs for the treatment of Alzheimer's disease belong to the group of inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors. However none of the drugs is able to combat or reverse the progression of the disease. Thus, the recently reported promising multitarget-directed molecule approach was applied here. Using the lead compound DUO3, which was found to be a potent inhibitor of the AChE and Butyrylcholinesterase (BuChE) as well as an inhibitor of the formation of the amyloid (Abeta) plaque, new non-permanently positively charged derivatives were synthesized and biologically characterized. In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are appropriate to cross the blood-brain barrier due to their pK(a) values and lipophilicity, and to inhibit both the AChE and BuChE. More important some of the pyridinylidene hydrazones inhibit the Abeta fibril formation completely and destruct the already formed fibrils significantly.
Poul Jacobsen - One of the best experts on this subject based on the ideXlab platform.
-
synthesis and structure activity relationship for a novel class of potent and selective carbamoyl triazole based inhibitors of hormone sensitive lipase
2004Co-Authors: Soren Ebdrup, Lotte G Sorensen, Ole Hvilsted Olsen, Poul JacobsenAbstract:The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in regulating fatty acid metabolism makes it an interesting pharmacological target for the treatment of insulin resistant and dyslipidemic disorders where a decrease in delivery of fatty acids to the circulation is desirable, e.g., in individuals with type 2 diabetes, metabolic syndrome, or impaired glucose tolerance. On the basis of a lead structure from high throughput screening, we have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As part of the lead optimization program, four new classes of carbamoyl-triazoles were synthesized and tested with respect to potency, efficacy and selectivity. Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL inhibitors. These compounds do not inhibit other hydrolases such as hepatic lipase, lipoprotein lipase, pancreatic lipase, and Butyrylcholine esterase. However, the inhibitors 4b and 4g with IC50 values for HSL of 0.17 and 0.25 μM, respect...
-
synthesis and structure activity relationship for a novel class of potent and selective carbamoyl triazole based inhibitors of hormone sensitive lipase
2004Co-Authors: Soren Ebdrup, Lotte G Sorensen, Ole Hvilsted Olsen, Poul JacobsenAbstract:The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in regulating fatty acid metabolism makes it an interesting pharmacological target for the treatment of insulin resistant and dyslipidemic disorders where a decrease in delivery of fatty acids to the circulation is desirable, e.g., in individuals with type 2 diabetes, metabolic syndrome, or impaired glucose tolerance. On the basis of a lead structure from high throughput screening, we have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As part of the lead optimization program, four new classes of carbamoyl-triazoles were synthesized and tested with respect to potency, efficacy and selectivity. Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL inhibitors. These compounds do not inhibit other hydrolases such as hepatic lipase, lipoprotein lipase, pancreatic lipase, and Butyrylcholine esterase. However, the inhibitors 4b and 4g with IC(50) values for HSL of 0.17 and 0.25 microM, respectively, were the only inhibitors selective against acetylcholine esterase. A reversible pseudosubstrate inhibition mechanism is proposed for this class of inhibitors.
Antonio Guerrieri - One of the best experts on this subject based on the ideXlab platform.
-
assay of serum cholinesterase activity by an amperometric biosensor based on a co crosslinked choline oxidase overoxidized polypyrrole bilayer
2018Co-Authors: Rosanna Ciriello, Sonia Lo Magro, Antonio GuerrieriAbstract:Based on choline oxidase immobilized by co-crosslinking on an overoxidised polypyrrole modified platinum electrode, a novel electrochemical assay for cholinesterase activity in human serum was developed. The assay was performed by adding an aliquot of cholinesterase standard solution or serum sample to phosphate buffer containing choline or thiocholine ester and measuring the oxidation current of hydrogen peroxide at the rotating modified electrode polarized at +0.7 V vs. SCE. The influence of some experimental parameters such as pH of the assay, mass transport at the electrode, type and concentration of the cholinesterase substrate was studied and optimised. Reversible inhibition of choline oxidase from cholinesterase substrates was evidenced for the first time, which increases in the order of acetylcholine, Butyrylcholine and s-butyrylthiocholine. Wide linear range, fast response time and appreciable long-term stability were assured for both acethyl- and Butyrylcholinesterase assays. On allowing the polypyrrole layer to efficiently remove interferences from the electroactive compounds in the sample, the present method revealed to be suitable for the detection of Butyrylcholinesterase in human serum at activities as low as 0.5 U L−1. The validation with a reference spectrophotometric method showed no significant differences when human serum samples were analysed.
Vildan Alptuzun - One of the best experts on this subject based on the ideXlab platform.
-
interaction of benzylidene hydrazono 1 4 dihydropyridines with β amyloid acetylcholine and Butyrylcholine esterases
2010Co-Authors: Vildan Alptuzun, Michaela Prinz, Verena Horr, Josef Scheiber, Krzysztof Radacki, Adyary Fallarero, Pia Vuorela, Bernd Engels, Holger Braunschweig, Ercin ErciyasAbstract:Abstract Approved drugs for the treatment of Alzheimer’s disease belong to the group of inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors. However none of the drugs is able to combat or reverse the progression of the disease. Thus, the recently reported promising multitarget-directed molecule approach was applied here. Using the lead compound DUO3, which was found to be a potent inhibitor of the AChE and Butyrylcholinesterase (BuChE) as well as an inhibitor of the formation of the amyloid (Aβ) plaque, new non-permanently positively charged derivatives were synthesized and biologically characterized. In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are appropriate to cross the blood–brain barrier due to their pKa values and lipophilicity, and to inhibit both the AChE and BuChE. More important some of the pyridinylidene hydrazones inhibit the Aβ fibril formation completely and destruct the already formed fibrils significantly.
-
interaction of benzylidene hydrazono 1 4 dihydropyridines with beta amyloid acetylcholine and Butyrylcholine esterases
2010Co-Authors: Vildan Alptuzun, Michaela Prinz, Verena Horr, Josef Scheiber, Krzysztof Radacki, Adyary Fallarero, Pia Vuorela, Bernd Engels, Holger Braunschweig, Ercin ErciyasAbstract:Approved drugs for the treatment of Alzheimer's disease belong to the group of inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors. However none of the drugs is able to combat or reverse the progression of the disease. Thus, the recently reported promising multitarget-directed molecule approach was applied here. Using the lead compound DUO3, which was found to be a potent inhibitor of the AChE and Butyrylcholinesterase (BuChE) as well as an inhibitor of the formation of the amyloid (Abeta) plaque, new non-permanently positively charged derivatives were synthesized and biologically characterized. In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are appropriate to cross the blood-brain barrier due to their pK(a) values and lipophilicity, and to inhibit both the AChE and BuChE. More important some of the pyridinylidene hydrazones inhibit the Abeta fibril formation completely and destruct the already formed fibrils significantly.
Soren Ebdrup - One of the best experts on this subject based on the ideXlab platform.
-
synthesis and structure activity relationship for a novel class of potent and selective carbamoyl triazole based inhibitors of hormone sensitive lipase
2004Co-Authors: Soren Ebdrup, Lotte G Sorensen, Ole Hvilsted Olsen, Poul JacobsenAbstract:The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in regulating fatty acid metabolism makes it an interesting pharmacological target for the treatment of insulin resistant and dyslipidemic disorders where a decrease in delivery of fatty acids to the circulation is desirable, e.g., in individuals with type 2 diabetes, metabolic syndrome, or impaired glucose tolerance. On the basis of a lead structure from high throughput screening, we have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As part of the lead optimization program, four new classes of carbamoyl-triazoles were synthesized and tested with respect to potency, efficacy and selectivity. Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL inhibitors. These compounds do not inhibit other hydrolases such as hepatic lipase, lipoprotein lipase, pancreatic lipase, and Butyrylcholine esterase. However, the inhibitors 4b and 4g with IC50 values for HSL of 0.17 and 0.25 μM, respect...
-
synthesis and structure activity relationship for a novel class of potent and selective carbamoyl triazole based inhibitors of hormone sensitive lipase
2004Co-Authors: Soren Ebdrup, Lotte G Sorensen, Ole Hvilsted Olsen, Poul JacobsenAbstract:The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in regulating fatty acid metabolism makes it an interesting pharmacological target for the treatment of insulin resistant and dyslipidemic disorders where a decrease in delivery of fatty acids to the circulation is desirable, e.g., in individuals with type 2 diabetes, metabolic syndrome, or impaired glucose tolerance. On the basis of a lead structure from high throughput screening, we have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As part of the lead optimization program, four new classes of carbamoyl-triazoles were synthesized and tested with respect to potency, efficacy and selectivity. Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL inhibitors. These compounds do not inhibit other hydrolases such as hepatic lipase, lipoprotein lipase, pancreatic lipase, and Butyrylcholine esterase. However, the inhibitors 4b and 4g with IC(50) values for HSL of 0.17 and 0.25 microM, respectively, were the only inhibitors selective against acetylcholine esterase. A reversible pseudosubstrate inhibition mechanism is proposed for this class of inhibitors.
