New derivatives of galanthamine containing peptide fragments with β-secretase inhibitor activity were synthesized. In position 6 of the galanthamine new shortened analogues of β-secretase inhibitor OM 99-2 (Boc-Val-Asn-Leu-Ala-OH and Boc-Val-Asn-Leu-Ala-Val-OH) were included. The new derivatives of the galanthamine in position 11 including Boc and norgalanthamine in P3 or P4 positions, Val in P2' position and benzylamin in P3'-position were also synthesized. All new peptides were investigated on mice for acute toxicity. The test compounds were administered to mice via intraperitoneal (i.p.) route. They have low toxicity (LD50>1000 mg/kg) after i.p. The compound 11-N-demethyl-11-N-N-[Boc-Asp(Asp-Leu-Ala-Val-NH-Bzl)]-Galanthamine was investigated by two way active avoidance method. The compound has good influence on the conditioned reflexes, which improved the processes of learning and memory. Inhibition activity of newly synthesized compounds was monitored against BuChE and IC50 values are determined. All compounds show activity in micromolar concentration. Compounds 5 and 6 have around 10 times higher activity than galanthamine. Compounds 4 and 9 also show good activity. All newly synthesized compounds show low acute toxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0929866522666150701111642 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and molecular docking analysis of novel hydrazone and thiosemicarbazide derivatives incorporating a pyrimidine ring: exploring neuroprotective activity.
J Biomol Struct Dyn
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul, Türkiye.
The increasing global prevalence of Alzheimer's disease necessitates the development of novel therapeutic approaches. Neurodegenerative diseases are associated with increased oxidative stress and levels of cholinesterase enzymes. Hence, the development of cholinesterase inhibitors and antioxidants may provide neuroprotective effects.
View Article and Find Full Text PDFDeoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure-activity relationship.
Arch Pharm (Weinheim)
January 2025
Department of Pharmacognosy, University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment.
View Article and Find Full Text PDFNaphthyl-functionalized acetamide derivatives: Promising agents for cholinesterase inhibition and antioxidant therapy in Alzheimer's disease.
Bioorg Chem
December 2024
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Concepción 4130000, Chile. Electronic address:
This study presents the synthesis and characterization of a series of 13 novel acetamides. These were subjected to Ellman's assay to determine the efficacy of the AChE and BChE inhibitors. Finally, we report their antioxidant activity as an alternative approach for the search for drugs to treat AD.
View Article and Find Full Text PDFDesign, Synthesis, Anticholinesterase and Antidiabetic Inhibitory Activities, and Molecular Docking of Novel Fluorinated Sulfonyl Hydrazones.
ACS Omega
October 2024
Department of Hair Care and Beauty Services, Yeşilyurt Vocational School, Malatya Turgut Özal University, Malatya 44210, Turkey.
In this study, it was aimed to synthesize ()-'-(2-hydroxybenzylidene)-substituted benzenesulfonohydrazide (-) from the 2-hydroxybenzaldehyde reaction of different substituted fluorinated sulfonyl hydrazides. The structures of the synthesized molecules were characterized by elemental analysis, FTIR, H NMR, C NMR, F NMR, and 2D NMR (HMBC, correlation spectroscopy, and HQSC). The anticholinesterase (AChE and BChE) and antidiabetic (α-glucosidase, α-amylase) inhibition activities of the synthesized compounds were evaluated.
View Article and Find Full Text PDFExploring the potential of in Alzheimer's disease treatment: An approach.
J Taibah Univ Med Sci
October 2024
Universitas Nasional, Department of Biology, South Jakarta, Indonesia.
Objectives: Alzheimer's disease (AD) is posing an increasing global threat and currently lacks effective treatments. Therefore, this study was aimed at exploring phytochemicals in () as inhibitors of acetylcholinesterase (AChE), β-site APP cleavage enzyme 1 (BACE1), and TNF-α converting enzyme (TACE) in AD. contains various bioactive compounds, such as chlorogenic acid, linalool, and catechins, which are known for their detoxification properties, capacity to resist and manage harmful moisture buildup, and therapeutic roles in COVID-19.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!