Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship DOI Open Access

A Gaur,

Yash Pal Singh, Rajiv Sharma

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 358(1)

Published: Dec. 27, 2024

Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases dementia. Although the exact pathophysiological causes AD remain unclear, its pathogenesis primarily driven by several distinct biochemical alterations: (i) accumulation toxic Aβ plaques, (ii) hyperphosphorylation tau proteins, (iii) oxidative stress resulting cell death, and (iv) an imbalance between two main neurotransmitters, glutamate acetylcholine (ACh). Currently, there are very few medications available no treatment. Presently marketed include memantine, N-methyl-d-aspartate receptor (NMDA) antagonist, acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, galantamine. Unfortunately, these only useful initial stages AD. The mentioned provide symptomatic relief do not slow down progression advanced stages. Therefore, urgent need to develop potential candidates treat AD, symptomatically therapeutically. Many research groups focus on natural products due their diverse therapeutic profiles easy availability. One such product deoxyvasicinone, isolated from Adhatoda vasica. Given broad pharmacological profile, various researchers have developed semisynthetic hybrids deoxyvasicinone address multifaceted diseases like In this review article, we tried summarize past decade (2014-2024) for managing We design, activity, structure-activity relationship (SAR) analysis. hope enhances reader's understanding future exploratory options management.

Language: Английский

Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease DOI Creative Commons
Willian Orlando Castillo Ordoñez, Nilza Velasco Palomino, Patrícia Varela

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: March 8, 2025

Abstract Patients with Alzheimer’s disease (AD) have two types of abnormal protein buildups: amyloid plaques and neurofibrillary tangles, in addition to the early synaptic dysfunction associated enzymes acetylcholinesterase (AChE) butyrylcholinesterase (BuChE). Impairment glutamatergic system is also crucial for neuronal survival, as it can cause that overstimulates glutamate receptors, especially N-methyl-d-aspartate receptors (NMDARs). Another affecting health glycogen synthase kinase-3 (GSK3), a widely preserved serine/threonine kinase linked disorders, including AD. In recent years, alkaloids from Amaryllidaceae received great attention their known anticholinergic activity, well antioxidant, antigenotoxic, neuroprotective properties. this context, identification compounds capable interacting different targets involved AD provides possible new therapeutic strategy. study, we conducted combination vitro silico approaches identify potential C. subedentata regulating key proteins Viability neuroprotection assays were performed evaluate exerted by extract against neurotoxicity induced Aβ (1–42) peptide Okadaic acid SH-SY5Y cells. Computational methods such docking molecular dynamic viability analysis explore interaction target (AChE, BuChE, NMDA, GSK-3) Our findings show exerts effects neurotoxic stimuli acid. addition, provide insight into how interact These insights action mechanisms these alkaloids. We hope rapid contribute bridge molecules counteract

Language: Английский

Citations

1
Repurposing Drugs: A Promising Therapeutic Approach against Alzheimer’s Disease DOI

Swagata Pattanaik,

Aruna Ghose,

Kakarla Pakeeraiah

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102698 - 102698

Published: Feb. 1, 2025

Language: Английский

Citations

0
Synthesis and biological evaluation of the Fluoro analog of Romidepsin with improved selectivity for class I histone deacetylases (HDACs) DOI

Xinluo Song,

Hanqi Wang, Ya Gao

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108348 - 108348

Published: March 13, 2025

Language: Английский

Citations

0
Exploring Pyridinium-Based Inhibitors of Cholinesterases: A Review of Synthesis, Efficacy, and Structural Insights DOI Creative Commons
Efraín Polo-Cuadrado,

Rojas-Peña Cristian,

A. Krogfelt Karen

et al.

European Journal of Medicinal Chemistry Reports, Journal Year: 2025, Volume and Issue: unknown, P. 100270 - 100270

Published: April 1, 2025

Language: Английский

Citations

0
Therapeutic Options in Alzheimer’s Disease: From Classic Acetylcholinesterase Inhibitors to Multi-Target Drugs with Pleiotropic Activity DOI Creative Commons
Ramón Cacabelos,

Olaia Martínez-Iglesias,

Natalia Cacabelos

et al.

Life, Journal Year: 2024, Volume and Issue: 14(12), P. 1555 - 1555

Published: Nov. 26, 2024

Alzheimer’s disease (AD) is a complex/multifactorial brain disorder involving hundreds of defective genes, epigenetic aberrations, cerebrovascular alterations, and environmental risk factors. The onset the neurodegenerative process triggered decades before first symptoms appear, probably due to combination genomic phenomena. Therefore, primary objective any effective treatment intercept in its presymptomatic phases. Since approval acetylcholinesterase inhibitors (Tacrine, Donepezil, Rivastigmine, Galantamine) Memantine, between 1993 2003, no new drug was approved by FDA until advent immunotherapy with Aducanumab 2021 Lecanemab 2023. Over past decade, more than 10,000 compounds potential action on some pathogenic components AD have been tested. limitations these anti-AD treatments stimulated search for multi-target (MT) drugs. In recent years, 1000 drugs MT function studied models. aim address complex multifactorial nature disease. This approach has offer comprehensive benefits single-target therapies, which may be limited their effectiveness intricate pathology AD. A strategy still unexplored agents. Another option could biotechnological products pleiotropic action, among nosustrophine-like represent an attractive, although not definitive, example.

Language: Английский

Citations

1
Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship DOI Open Access

A Gaur,

Yash Pal Singh, Rajiv Sharma

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 358(1)

Published: Dec. 27, 2024

Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases dementia. Although the exact pathophysiological causes AD remain unclear, its pathogenesis primarily driven by several distinct biochemical alterations: (i) accumulation toxic Aβ plaques, (ii) hyperphosphorylation tau proteins, (iii) oxidative stress resulting cell death, and (iv) an imbalance between two main neurotransmitters, glutamate acetylcholine (ACh). Currently, there are very few medications available no treatment. Presently marketed include memantine, N-methyl-d-aspartate receptor (NMDA) antagonist, acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, galantamine. Unfortunately, these only useful initial stages AD. The mentioned provide symptomatic relief do not slow down progression advanced stages. Therefore, urgent need to develop potential candidates treat AD, symptomatically therapeutically. Many research groups focus on natural products due their diverse therapeutic profiles easy availability. One such product deoxyvasicinone, isolated from Adhatoda vasica. Given broad pharmacological profile, various researchers have developed semisynthetic hybrids deoxyvasicinone address multifaceted diseases like In this review article, we tried summarize past decade (2014-2024) for managing We design, activity, structure-activity relationship (SAR) analysis. hope enhances reader's understanding future exploratory options management.

Language: Английский

Citations

0