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

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 272, P. 132748 - 132748

Published: May 29, 2024

Language: Английский

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 Creative Commons
Dong Xie, Yun Tian, Li Cao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 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.

Language: Английский

Citations

0
From Dyrk1A inhibitors to a novel class of antiviral agents: Targeting Enterovirus EV-A71 with 2-aryl-substituted thiophene scaffolds DOI Creative Commons

Parthiena M Keddis,

Tuong-Khanh My Tu,

Hugo Scherer

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117348 - 117348

Published: Feb. 4, 2025

Language: Английский

Citations

0
Morpholino Pyridazinone Derivatives as Selective Mao-B Inhibitors DOI
Yaren Nur Zenni, Zeynep Özdemir, Selma Saraç

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Alpha-synuclein aggregation in Parkinson’s disease DOI

I. Silva,

Manuele Figueiredo da Silva,

Thiago Santos de Assis Dutra

et al.

Advances in protein chemistry and structural biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Inhibition of Monoamine Oxidases by Pyridazinobenzylpiperidine Derivatives DOI Creative Commons
Jong‐Min Oh, Yaren Nur Zenni, Zeynep Özdemir

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3097 - 3097

Published: June 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.

Language: Английский

Citations

1
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

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 272, P. 132748 - 132748

Published: May 29, 2024

Language: Английский

Citations

0