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

Safety issues of donepezil combined with memantine in Alzheimer’s disease population: real-world pharmacovigilance DOI
Yi Zeng,

Bingshuo Liu,

Lisi Zhou

et al.

Expert Opinion on Drug Safety, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Alzheimer's disease (AD) is the most common form of dementia. The combination Donepezil and Memantine only FDA-approved therapy for AD, but its adverse drug reactions (ADRs) lack systematic analysis. This study carried out analysis AD population to provide evidence support clinical safety use. Using FAERS database reports (January 2004-January 2024) with as primary suspected drugs, four disproportionality methods - ROR, PRR, BCPNN, EBGM were applied identify positive ADR signals. Subgroup analyses conducted by age gender. A total 712 analyzed (54.6% female, 55.1% aged 65-85). Across population, 42 ADRs identified, including hypertensive crisis, hyperglycemia, hyperosmolar nonketotic syndrome, proteinuria, hydronephrosis, many which newly reported. revealed prostate hypertrophy, acute kidney injury, cerebral infarction in males, while females experienced more severe cardiovascular events, such complete AV block ventricular extrasystole. Additional included hyperkalemia, sinus bradycardia, extrapyramidal disorders. Despite partial consistency combined instructions, new signals emerged, significant differences subgroups.

Language: Английский

Citations

1
Anti-Orthopoxvirus Activity of Amantadine and Rimantadine Derivatives—In Vitro Testing and Molecular Modeling DOI Creative Commons

Ivan A. Moskalev,

Е. А. Akishina, Е. А. Дикусар

et al.

Chemistry, Journal Year: 2025, Volume and Issue: 7(2), P. 34 - 34

Published: March 1, 2025

In 2022, the number of mpox cases spiked worldwide, leading to a surge in scientific research on members Orthopoxvirus genus and discovery new compounds exhibiting anti-orthopoxvirus activity. This work is devoted synthesis containing an adamantane fragment evaluation their activity against vaccinia virus, offering possible mechanism antiviral action synthesized agents. Among all studied derivatives, three (2, 4, 12) were found demonstrate highest activity, with most promising compound 2 (N-(adamantan-1-yl)isonicotinamide) having lowest toxicity level selectivity index (SI) 115. The pharmacophoric profiles these are similar profile tecovirimat, inhibitor membrane viral protein p37. Analysis results molecular modeling suggests that investigated can inhibit virus by suppressing phospholipase

Language: Английский

Citations

0
Preparation of Acetylcholinesterase Inhibitory Peptides from Yellowfin Tuna Pancreas Using Moderate Ultrasound-Assisted Enzymatic Hydrolysis DOI Creative Commons
Pai Peng, Hui Yu,

Meiting Xian

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(2), P. 75 - 75

Published: Feb. 9, 2025

Bioactive peptides represent a promising therapeutic approach for Alzheimer's disease (AD) by maintaining cholinergic system homeostasis through the inhibition of acetylcholinesterase (AChE) activity. This study focused on extracting AChE inhibitory from yellowfin tuna pancreas using moderate ultrasound-assisted enzymatic hydrolysis (MUE). Firstly, papain and MUE stood out five enzymes four methods, respectively, comparing degree activity different pancreatic protein hydrolysates. Subsequently, optimal conditions were obtained single-factor, Plackett-Burman, response surface methodologies. The hydrolysate prepared under was then purified ultrafiltration followed RP-HPLC, which novel peptide (LLDF) identified LC-MS/MS virtual screening. LLDF effectively inhibited competitive mechanism, with an IC50 18.44 ± 0.24 μM. Molecular docking molecular dynamic simulation revealed that bound robustly to active site via hydrogen bonds. These findings provided theoretical basis valuable use introduced new viewpoint potential advantages future AD treatment.

Language: Английский

Citations

0
Harnessing Marine Resources for Alzheimer’s Therapy: A Review Integrating Bioactivity and Molecular Docking DOI

Hinnan Khalid,

Hassan Mohamed,

Adel Elthoukhy

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177611 - 177611

Published: April 1, 2025

Language: Английский

Citations

0
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