Τhiazolidine-4-One Derivatives with Variable Modes of Inhibitory Action Against DPP4, a Drug Target with Multiple Activities and Established Role in Diabetes Mellitus Type II DOI Creative Commons
Dionysia Amanatidou, Phaedra Eleftheriou, Anthi Petrou

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 52 - 52

Опубликована: Янв. 4, 2025

Background/Objectives: DPP4 is an enzyme with multiple natural substrates and probable involvement in various mechanisms. It constitutes a drug target for the treatment of diabetes II, although, also related to other disorders. While number drugs competitive inhibitory action covalent binding capacity are available, undesired side effects exist partly attributed kinetics, research finding novel, potent, safer compounds continues. Despite research, low uncompetitive non-competitive inhibitors, which could be worth pharmaceutical mechanism studies, was mentioned. Methods: In present study sixteen 3-(benzo[d]thiazol-2-yl)-2-aryl thiazolidin-4-ones were selected evaluation, based on structural characteristics docking analysis tested vitro using H-Gly-Pro-amidomethyl coumarin substrate. Their mode inhibition explored. Results: Twelve exhibited IC50 values at nM range best showing = 12 ± 0.5 nM, better than sitagliptin. Most inhibition. Inhibition modes uncompetitive, non-competitive, mixed type identified. Docking accordance results, linear correlation logIC50 Probability Binding Factor(PF) derived specific box whole enzyme. According two sites inhibitors highlighted wider area active site propeller loop. Conclusions: Potent competitive, action, one sitagliptin, found. used estimate ways binding. However, crystallographic or NMR studies needed elucidate exact way especially inhibitors.

Язык: Английский

Τhiazolidine-4-One Derivatives with Variable Modes of Inhibitory Action Against DPP4, a Drug Target with Multiple Activities and Established Role in Diabetes Mellitus Type II DOI Creative Commons
Dionysia Amanatidou, Phaedra Eleftheriou, Anthi Petrou

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 52 - 52

Опубликована: Янв. 4, 2025

Background/Objectives: DPP4 is an enzyme with multiple natural substrates and probable involvement in various mechanisms. It constitutes a drug target for the treatment of diabetes II, although, also related to other disorders. While number drugs competitive inhibitory action covalent binding capacity are available, undesired side effects exist partly attributed kinetics, research finding novel, potent, safer compounds continues. Despite research, low uncompetitive non-competitive inhibitors, which could be worth pharmaceutical mechanism studies, was mentioned. Methods: In present study sixteen 3-(benzo[d]thiazol-2-yl)-2-aryl thiazolidin-4-ones were selected evaluation, based on structural characteristics docking analysis tested vitro using H-Gly-Pro-amidomethyl coumarin substrate. Their mode inhibition explored. Results: Twelve exhibited IC50 values at nM range best showing = 12 ± 0.5 nM, better than sitagliptin. Most inhibition. Inhibition modes uncompetitive, non-competitive, mixed type identified. Docking accordance results, linear correlation logIC50 Probability Binding Factor(PF) derived specific box whole enzyme. According two sites inhibitors highlighted wider area active site propeller loop. Conclusions: Potent competitive, action, one sitagliptin, found. used estimate ways binding. However, crystallographic or NMR studies needed elucidate exact way especially inhibitors.

Язык: Английский

Процитировано

0