Trimethoxylated Halogenated Chalcones as Dual Inhibitors of MAO-B and BACE-1 for the Treatment of Neurodegenerative Disorders DOI Creative Commons

Vishal Payyalot Vishal,

Jong‐Min Oh, Ahmed Khames

et al.

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(6), P. 850 - 850

Published: June 8, 2021

Six halogenated trimethoxy chalcone derivatives (CH1–CH6) were synthesized and spectrally characterized. The compounds further evaluated for their inhibitory potential against monoamine oxidases (MAOs) β-secretase (BACE-1). inhibited MAO-B more effectively than MAO-A, the 2′,3′,4′-methoxy moiety in CH4–CH6 was effective inhibition 2′,4′,6′-methoxy CH1–CH3. Compound CH5 most potently MAO-B, with an IC50 value of 0.46 µM, followed by CH4 (IC50 = 0.84 µM). In (CH4-CH6), order –Br > -Cl -F CH6 at para-position ring B chalcone. selective selectivity index (SI) values 15.1 31.3, respectively, over MAO-A. moderately BACE-1 13.6 19.8 respectively. When assessed cell viability studies on normal African Green Monkey kidney line (VERO) using MTT assays, it noted that both found to be safe, only a slightly toxic effect observed concentrations above 200 µg/mL. decreased reactive oxygen species (ROS) levels VERO cells treated H2O2, indicating retained protective effects antioxidant activities. All showed high blood brain barrier permeabilities analyzed parallel artificial membrane permeability assay (PAMPA). Molecular docking ADME prediction lead provided insights into rationale behind binding CNS drug likeness. From non-test mutagenicity cardiotoxicity studies, non-mutagenic non-/weak-cardiotoxic. These results suggest could considered candidates cure neurological dysfunctions.

Language: Английский

Antioxidants in Anti-Alzheimer's Disease Drug Discovery DOI

Jianan Guo,

Yalan Zhu,

Jia Zhi

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 107, P. 102707 - 102707

Published: Feb. 27, 2025

Language: Английский

Citations

1
One-pot synthesis and molecular docking of some new spiropyranindol-2-one derivatives as immunomodulatory agents and in vitro antimicrobial potential with DNA gyrase inhibitor DOI
Mohamed A. Salem, Ahmed Ragab, Ahmed Askar

et al.

European Journal of Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 188, P. 111977 - 111977

Published: Dec. 24, 2019

Language: Английский

Citations

73
Synthesis of novel organohalogen chalcone derivatives and screening of their molecular docking study and some enzymes inhibition effects DOI
Serdar Burmaoğlu, Elif Akın Kazancıoğlu,

Rüya Kaya

et al.

Journal of Molecular Structure, Journal Year: 2020, Volume and Issue: 1208, P. 127868 - 127868

Published: Feb. 13, 2020

Language: Английский

Citations

50
The molecular mechanism, targets, and novel molecules in the treatment of Alzheimer’s disease DOI
Akash Verma,

Digambar Kumar Waiker,

Bhagwati Bhardwaj

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 119, P. 105562 - 105562

Published: Dec. 16, 2021

Language: Английский

Citations

47
Latest advances in dual inhibitors of acetylcholinesterase and monoamine oxidase B against Alzheimer’s disease DOI Creative Commons

Da-Jiang Zou,

Renzheng Liu,

Yangjing Lv

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Nov. 13, 2023

Alzheimer's disease (AD) is a progressive brain characterised by memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered contribute pathologies Therefore, we reviewed dual (AChE) MAO-B developed in last five years. In this review, these dual-target were classified into six groups according basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine hydrazine, other scaffolds. Their design strategies, structure-activity relationships (SARs), molecular docking studies with AChE analysed discussed, giving valuable insights subsequent development inhibitors. Challenges balanced potent noted, corresponding solutions provided.

Language: Английский

Citations

22
Design, synthesis and evaluation of quinoline- O -carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease DOI Creative Commons
Hongsong Chen,

Jing Mi,

Sen Li

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Jan. 23, 2023

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated AChE/BuChE inhibition anti-inflammatory property. in vitro activities showed that compound 3f a reversible dual eeAChE/eqBuChE inhibitor with IC50 values 1.3 µM 0.81 µM, respectively. Moreover, displayed good property decreasing the production IL-6, IL-1β NO. In addition, presented significant neuroprotective effect on Aβ25-35-induced PC12 cell injury. Furthermore, stabilities artificial gastrointestinal fluids, liver microsomes plasma. could improve AlCl3-induced zebrafish AD model increasing level ACh. Therefore, promising multifunctional agent treatment AD.

Language: Английский

Citations

20
Development of the “hidden” multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease DOI
Rui Chen, Xinjuan Li, Hongsong Chen

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 251, P. 115253 - 115253

Published: March 10, 2023

Language: Английский

Citations

19
1-Benzylpyrrolidine-3-amine-based BuChE inhibitors with anti-aggregating, antioxidant and metal-chelating properties as multifunctional agents against Alzheimer’s disease DOI
Tomasz Wichur, Anna Więckowska, Krzysztof Więckowski

et al.

European Journal of Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 187, P. 111916 - 111916

Published: Nov. 26, 2019

Language: Английский

Citations

48
Calycosin and 8-O-methylretusin isolated from Maackia amurensis as potent and selective reversible inhibitors of human monoamine oxidase-B DOI
Jong‐Min Oh, Hyun‐Jae Jang,

Won Jun Kim

et al.

International Journal of Biological Macromolecules, Journal Year: 2020, Volume and Issue: 151, P. 441 - 448

Published: Feb. 19, 2020

Language: Английский

Citations

43
Halogenated Coumarin–Chalcones as Multifunctional Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors DOI Creative Commons

Nisha Abdul Rehuman,

Jong‐Min Oh, Lekshmi R. Nath

et al.

ACS Omega, Journal Year: 2021, Volume and Issue: 6(42), P. 28182 - 28193

Published: Oct. 12, 2021

A series of halogenated coumarin-chalcones were synthesized, characterized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) evaluated. Compound CC2 most potently inhibited MAO-B with an IC50 value 0.51 μM, followed by CC1 (IC50 = 0.69 μM), a selectivity index (SI) >78.4 >58.0, respectively, over MAO-A. However, none the compounds effectively MAO-A, AChE, BChE, except for CC3 inhibiting BChE values 7.00 (SI > 5.73 AChE) 11.8 respectively. found to be reversible competitive inhibitors MAO-B, Ki 0.50 ± 0.06 0.53 0.04 was also inhibitor 2.84 0.09 μM. The parallel artificial membrane permeability assay (PAMPA) method showed that lead candidates can cross blood-brain barrier (BBB). in vitro toxicity analysis on Vero cell line (Normal African green monkey kidney epithelial cells) MTT confirmed both nontoxic up 100 μg/mL, which is almost equivalent times effective concentration used biological studies. In addition, attenuated H2O2-induced cellular damage via reactive oxygen species (ROS) scavenging effect. These results suggest are selective BChE. Molecular docking studies provided possible type interactions targeted enzymes. Based findings, compounds, CC2, considered plausible drug neurodegenerative disorders.

Language: Английский

Citations

39