Oxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics

Complementary Therapies in Medicine, Journal Year: 2019, Volume and Issue: 49, P. 102294 - 102294

Published: Dec. 31, 2019

Language: Английский

---

Alzheimer's disease: Updated multi-targets therapeutics are in clinical and in progress

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 238, P. 114464 - 114464

Published: May 20, 2022

Language: Английский

---

Advancements in the development of multi-target directed ligands for the treatment of Alzheimer’s disease

Bioorganic & Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 61, P. 116742 - 116742

Published: April 5, 2022

Language: Английский

---

Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents

Molecules, Journal Year: 2024, Volume and Issue: 29(9), P. 2127 - 2127

Published: May 3, 2024

Neurodegeneration is a gradual decay process leading to the depletion of neurons in both central and peripheral nervous systems, ultimately resulting cognitive dysfunctions deterioration brain functions, alongside decline motor skills behavioral capabilities. Neurodegenerative disorders (NDs) impose substantial socio-economic strain on society, aggravated by advancing age world population absence effective remedies, predicting negative future. In this context, urgency discovering viable therapies critical and, despite significant efforts medicinal chemists developing potential drug candidates exploring various small molecules as therapeutics, regrettably, truly treatment yet be found. Nitrogen heterocyclic compounds, particularly those containing indole nucleus, which has emerged privileged scaffold, have attracted particular attention for variety pharmacological applications. This review analyzes rational design strategy adopted different research groups development anti-neurodegenerative indole-based compounds modulate molecular targets involved NDs, with reference most recent advances between 2018 2023.

Language: Английский

---

From combinations to multitarget‐directed ligands: A continuum in Alzheimer's disease polypharmacology

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(5), P. 2606 - 2633

Published: June 19, 2020

The continued drug discovery failures in complex neurodegenerative diseases, including Alzheimer's disease (AD), has raised questions about the classical paradigm "one-drug, one-target, one-disease." In parallel, ever-increasing awareness of multiplicity underlying pathways led to affirmation polypharmacological approaches. Polypharmacology, which broadly embodies use pharmaceutical agents acting on multiple targets, seems be best way restore diseased network and provide disease-modifying effects AD. this review, our aim is a roadmap into world that still only partly explored should seen as continuum pharmacological opportunities, from combinations multitarget-directed ligands (both codrugs hybrids). Each modality unique features can effectively exploited by medicinal chemists. We argue understanding their advantages drawbacks very helpful choosing proper approach developing successful AD multitarget drug-discovery endeavors. also briefly dwell (co)target validation, an aspect quite often neglected, but critical for efficient clinical translation. substantiate discussion with instructive examples taken recent literature. Our wish that, spite specter high attrition rates, researchers preferring enter, stay, progress field would help grow sector develop polypharmacology full potential.

Language: Английский

---

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(2), P. 858 - 901

Published: Oct. 25, 2020

Abstract Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe effective in treating organophosphorus (OPs) poisoning completed Phase 1 2 pharmacokinetic (PK) safety studies. The introduction specific mutations into native to endow it a self‐reactivating property gained much progress producing OPs hydrolases. hydrolysis ability on cocaine confirmed but was blocked clinical application due poor PK properties. Several mutants elevated activity were published, some which have shown efficiency addiction human. increased level progressed Alzheimer's disease patients made promising target elevate acetylcholine attenuate cognitive status. A variety selective inhibitors high inhibitory published recent years reviewed could influence the weight insulin secretion resistance knockout (KO) mice through hydrolyzing ghrelin. BChE‐ghrelin pathway also regulate aggressive behaviors BChE‐KO mice.

Language: Английский

---

Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 240, P. 114606 - 114606

Published: July 16, 2022

Language: Английский

---

Tacrine-Based Hybrids: Past, Present, and Future

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1717 - 1717

Published: Jan. 15, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder which characterized by β-amyloid (Aβ) aggregation, τ-hyperphosphorylation, and loss of cholinergic neurons. The other important hallmarks AD are oxidative stress, metal dyshomeostasis, inflammation, cell cycle dysregulation. Multiple therapeutic targets may be proposed for the development anti-AD drugs, “one drug–multiple targets” strategy current interest. Tacrine (THA) was first clinically approved cholinesterase (ChE) inhibitor, withdrawn due to high hepatotoxicity. However, its potency in ChE inhibition, low molecular weight, simple structure make THA promising scaffold developing multi-target agents. In this review, we summarized THA-based hybrids published from 2006 2022, thus providing an overview strategies that have been used drug design approaches resulted significant cognitive improvements reduced

Language: Английский

---

TMF Attenuates Cognitive Impairment and Neuroinflammation by Inhibiting the MAPK/NF-κB Pathway in Alzheimer’s Disease: A Multi-Omics Analysis

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(2), P. 74 - 74

Published: Feb. 7, 2025

The rising prevalence of Alzheimer's disease (AD) underscores the urgent need for novel therapeutic agents derived from natural sources. Among flavonoids, 3',4',5,7-tetramethoxyflavone (TMF), a structural analog luteolin, has gained attention its favorable pharmacokinetics and potential neuroprotective properties. Despite significant effects TMF, efficacy mechanism action in AD remain unclear. This study explored TMF's pharmacological models, highlighting ability to improve memory cognitive deficits APP/PS1 mice. TMF reduced Aβ plaques, NFTs formation, glial activation while suppressing neuroinflammation through MAPK/NF-κB pathway. Further analysis LPS-induced BV2 cells revealed reduce microglial activation. These findings highlight anti-neuroinflammatory activity suggesting as treatment AD.

Language: Английский

---

Novel tacrine–benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer’s Disease

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 35(1), P. 211 - 226

Published: Nov. 25, 2019

Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based repositioning well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling benzofuran (BF) derivatives. The BF framework aims endow conjugate molecules with ability for inhibition AChE (bimodal way) amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating concomitant extra anti-oxidant activity, hydroxyl substitution. TAC-BF conjugates showed very good activity (sub-micromolar range) capacity self- Cu-mediated Aβ dependence linker size substituent groups each main moiety. Neuroprotective effects were also found compounds through viability assays neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights best structural parameters, take in consideration future studies view potential applications AD therapy.

Language: Английский

---