Last update 01 Nov 2024

BChE x BACE1 x AChE

Last update 01 Nov 2024

Basic Info

Related Targets

BChEBACE1AChE

Drugs associated with BChE x BACE1 x AChE

SB-1448

Target

AChE x BACE1 x BChE

Mechanism

AChE inhibitors [+2]

Active Org.

Indian Institute of Integrative Medicine

Originator Org.

Indian Institute of Integrative Medicine

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BChE x BACE1 x AChE

100 Translational Medicine associated with BChE x BACE1 x AChE

0 Patents (Medical) associated with BChE x BACE1 x AChE

Literatures (Medical) associated with BChE x BACE1 x AChE

01 Nov 2024·Bioorganic & Medicinal Chemistry Letters

Synthesis and biological evaluation of novel aminoquinolines with an n-octyl linker: Impact of halogen substituents on C(7) or a terminal amino group on anticholinesterase and BACE1 activity

Article

Author: Zandona, Antonio ; Matošević, Ana ; Bosak, Anita ; Opsenica, Dejan ; Bartolić, Marija ; Petrić, Rajo ; Maraković, Nikola

Alzheimer's disease is age-related multifactorial neurodegenerative disease manifested by gradual loss of memory, cognitive decline and changes in personality. Due to rapid and continuous growth of its prevalence, the treatment of Alzheimer's disease calls for development of new and efficacies drugs, especially those that could be able to simultaneously act on more than one of possible targets of action. Aminoquinolines have proven to be a highly promising structural scaffold in the design of such a drug as cholinesterases and β-secretase 1 inhibitors. In this study, we synthesised twenty-two new 4-aminoquinolines with different halogen atom and its position in the terminal N-benzyl group or with a trifluoromethyl or a chlorine as C(7)-substituents on the quinoline moiety. All compounds were evaluated as multi-target-directedligands by determining their inhibition potency towards human acetylcholinesterase, butyrylcholinesterase and β-secretase 1. All of the tested derivatives were very potent inhibitors of human acetylcholinesterase and butyrylcholinesterase with inhibition constants (K_i) in the nM to low μM range. Most were estimated to be able to cross the blood-brain barrier by passive transport and were nontoxic toward cells that represented the main models of individual organs.

10 Sep 2024·Scientific reports

Synthesis, biological evaluation and molecular modeling studies of methyl indole-isoxazole carbohydrazide derivatives as multi-target anti-Alzheimer's agents.

Article

Author: Iraji, Aida ; Saeedi, Mina ; Nazari Montazer, Mohammad ; Karimi, Mona ; Nikfar, Parisa ; Mirfazli, Seyedeh Sara ; Edraki, Najmeh

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, ¹H NMR, and ¹³C NMR as well as mass spectrometry and elemental analysis. All derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Out of all synthesized compounds, compound 5d exhibited the highest potency as AChE inhibitor with an IC₅₀ value of 29.46 ± 0.31 µM. It showed significant selectivity towards AChE, with no notable inhibition against BuChE. A kinetic study on AChE for compound 5d indicated a competitive inhibition pattern. Also, 5d exhibited promising BACE1 inhibitory potential with an IC₅₀ value of 2.85 ± 0.09 µM and in vitro metal chelating ability against Fe³⁺. The molecular dynamic studies of 5d against both AChE and BACE1 were executed to evaluate the behavior of this derivative in the binding site. The results showed that the new compounds deserve further chemical optimization to be considered potential anti-AD agents.

01 Sep 2024·Heliyon

Multi-modal neuroprotection of Argemone mexicana L. against Alzheimer’s disease: In vitro and in silico study

Article

Author: Akhter, Shahina ; Ahammad, Foysal ; Islam, Md. Saidul ; Uddin, Mohammad Jashim ; Aktar, Asmim ; Rahman, Md. Mashiar ; Rahman, Md Mashiar ; Khan, Mala ; Talukder, Md Enamul Kabir ; Afroze, Mirola ; Islam, Md Saidul ; Laboni, Aysha Akter ; Talukder, Md. Enamul Kabir

Argemone mexicana L. is a medicinal plant, but its impact on Alzheimer's disease (AD) is right now undetermined. We intended to investigate the in-vitro anti-AD potential of leaves and flowers of A. mexicana methanol, ethanol, and ethyl extracts and to identify multi-modal anti-AD phytochemicals by computational approaches. Molecular docking of 196 phytochemicals identified three hit phytochemicals (protoberberine, protopine, and codeine) with higher binding affinity and multi-targeting ability toward AChE, BChE, BACE-1, and GSK-3β. Further MM-GBSA assays confirmed the integrity of these phytochemicals as the hit phytochemicals. However, these phytochemicals demonstrated favorable pharmacokinetics (PK) and drugable properties having no toxicity. Molecular dynamics simulations confirmed the binding strength of the hit phytoconstituents in the active pockets of AChE, BChE, BACE-1, and GSK-3β with multi-targeting inhibitory activities. All the extracts exhibited dose-dependent antioxidant and anti-cholinesterase activities supporting the in silico results in the context of oxidative stress and cholinergic pathways. Our results offer scientific validation of the anti-AD properties of Argemone mexicana L. and identified protoberberine, protopine, and codeine that could be used for the development of multi-modal inhibitors of AChE, BChE, BACE-1, and GSK-3β to combat AD. Additional in vivo validation is recommended to ensure a thorough assessment in the present research.

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