Cited by Design and discovery of anthranilamide derivatives as a potential treatment for neurodegenerative disorders via targeting cholinesterases and monoamine oxidases

3D-QSAR, design, molecular docking and dynamics simulation studies of novel 6-hydroxybenzothiazole-2-carboxamides as potentially potent and selective monoamine oxidase B inhibitors DOI

Dong Xie, Yun Tian, Li Cao

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 28, 2025

6-hydroxybenzothiazole-2-carboxamide is a novel, potent and specific inhibitor of monoamine oxidase B (MAO-B), which can be used to study the molecular structure develop new neuroprotective strategies. The aim this was create an effective predictive model from derivatives provide reliable basis for development MAO-B inhibitors treatment neurodegenerative diseases. First, compounds were constructed optimized using ChemDraw Sybyl-X software. Subsequently, QSAR modeling performed COMSIA method in predict IC50 values set novel derivatives. ten most promising screened based on tested docking. Finally, binding stability dynamic behavior these with receptors analyzed by dynamics simulation (MD). 3D-QSAR showed good ability, q2 value 0.569, r2 0.915, SEE 0.109 F 52.714 model. Based model, we designed series 6-HBC predicted their Among them, compound 31.j3 exhibited highest obtained score docking test. MD results that stable receptor, RMSD fluctuated between 1.0 2.0 Å, indicating its conformational stability. In addition, energy decomposition analysis revealed contribution key amino acid residues energy, especially Van der Waals interactions electrostatic play important role stabilizing complex. study, potential as systematically investigated 3D-QSAR, simulations. successfully not only demonstrated efficient inhibitory activity, but also verified receptor simulation, provides strong support therapeutic drugs These findings theoretical practical guidance future drug design experimental validation.

Язык: Английский

Процитировано

From Dyrk1A inhibitors to a novel class of antiviral agents: Targeting Enterovirus EV-A71 with 2-aryl-substituted thiophene scaffolds DOI

Parthiena M Keddis,

Tuong-Khanh My Tu,

Hugo Scherer

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 287, С. 117348 - 117348

Опубликована: Фев. 4, 2025

Язык: Английский

Процитировано

Morpholino Pyridazinone Derivatives as Selective Mao-B Inhibitors DOI

Yaren Nur Zenni, Zeynep Özdemir, Selma Saraç

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

Alpha-synuclein aggregation in Parkinson’s disease DOI

I. Silva,

Manuele Figueiredo da Silva,

Thiago Santos de Assis Dutra

и другие.

Advances in protein chemistry and structural biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

Inhibition of Monoamine Oxidases by Pyridazinobenzylpiperidine Derivatives DOI

Jong‐Min Oh, Yaren Nur Zenni, Zeynep Özdemir

и другие.

Molecules, Год журнала: 2024, Номер 29(13), С. 3097 - 3097

Опубликована: Июнь 28, 2024

Monoamine oxidase inhibitors (MAOIs) have been crucial in the search for anti-neurodegenerative medications and continued to be a vital source of molecular mechanistic diversity. Therefore, selective MAOIs is one main areas current drug development. To increase effectiveness safety treating Parkinson’s disease, new scaffolds reversible MAO-B are being developed. A total 24 pyridazinobenzylpiperidine derivatives were synthesized evaluated MAO. Most compounds showed higher inhibition than MAO-A. Compound S5 most potently inhibited with an IC50 value 0.203 μM, followed by S16 (IC50 = 0.979 μM). In contrast, all weak MAO-A inhibition. Among them, S15 3.691 3.857 had highest selectivity index (SI) 19.04 compared (3-Cl) greater other substituents -Cl > -OCH3 -F -CN -CH3 -Br at 3-position. However, 2- 4-position low inhibition, except (2-CN). addition, containing two or more exhibited kinetic study, Ki values 0.155 ± 0.050 0.721 0.074 respectively, competitive reversible-type Additionally, PAMPA, both lead demonstrated blood–brain barrier penetration. Furthermore, stability was 2V5Z-S5 complex pi–pi stacking Tyr398 Tyr326. These results suggest that potent, reversible, can used as potential agents treatment neurological disorders.

Язык: Английский

Процитировано

Design and discovery of anthranilamide derivatives as a potential treatment for neurodegenerative disorders via targeting cholinesterases and monoamine oxidases DOI

Sumera Zaib, Imtiaz Khan, Hafiz Saqib Ali

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 272, С. 132748 - 132748

Опубликована: Май 29, 2024

Язык: Английский

Процитировано