Background: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.
Methods: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.
Results: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).
Conclusions: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197562 | PMC |
| http://dx.doi.org/10.1186/1472-6882-11-79 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhanced prediction of beta-secretase inhibitory compounds with mol2vec technique and machine learning algorithms.
SAR QSAR Environ Res
December 2024
Department of Pharmacognosy, Faculty of Pharmacognosy and Traditional Medicine, Hanoi University of Pharmacy, Hanoi, Vietnam.
A comprehensive computational strategy that combined QSAR modelling, molecular docking, and ADMET analysis was used to discover potential inhibitors for β-secretase 1 (BACE-1). A dataset of 1,138 compounds with established BACE-1 inhibitory activities was used to build a QSAR model using mol2vec descriptors and support vector regression. The obtained model demonstrated strong predictive performance (training set: = 0.
View Article and Find Full Text PDFMagnesium-Phenolic Nanoeditor Refining Gliomatous T Cells for Metalloimmunotherapy.
ACS Nano
December 2024
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
More than the sparse infiltration in glioblastoma, cytotoxic T lymphocytes (CTLs) also function inefficiently and overexpress the inhibitory markers, especially the identified NK cell receptor (NK1.1). However, most studies solely focus on how to augment tumor-infiltrating CTLs and overlook their killing maintenance.
View Article and Find Full Text PDFInhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation.
Int J Mol Sci
December 2024
Department of Nutrition, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City 40604, Taiwan.
Alzheimer's disease (AD), a leading neurodegenerative disorder, is closely associated with the accumulation of amyloid-beta (Aβ) peptides in the brain. The enzyme β-secretase (BACE1), pivotal in Aβ production, represents a promising therapeutic target for AD. While bioactive peptides derived from food protein hydrolysates have neuroprotective properties, their inhibitory effects on BACE1 remain largely unexplored.
View Article and Find Full Text PDFStructure-Based Virtual Screening and Biological Characterization of Novel BACE-1 and Amyloid-β Aggregation Inhibitors.
ChemMedChem
December 2024
Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
Alzheimer's disease (AD) is a complex neurodegenerative disorder having limited treatment options. The beta-site APP cleaving enzyme 1 (BACE-1) is a key target for therapeutic intervention in Alzheimer's disease. To discover new scaffolds for BACE-1 inhibitors, a ChemBridge DIVERSet library of 20,000 small molecules was employed to structure-based virtual screening.
View Article and Find Full Text PDFSmall molecule inhibits BACE1 activity by a dual mechanism confirmed by simulations-based study.
J Biomol Struct Dyn
December 2024
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Article Synopsis
- Alzheimer's disease (AD) is a serious neurodegenerative disorder marked by amyloid-beta plaques and neurofibrillary tangles, and it's primarily initiated by the action of the enzyme BACE1 on amyloid precursor protein (APP).
- Researchers have discovered a small molecule that appears to effectively inhibit BACE1 by fitting well into its active site, outperforming the known drug Umibecestat (CNP-520) in terms of binding orientation and blocking the enzyme's activity.
- The study utilized advanced techniques like virtual high-throughput screening and molecular dynamics simulations to identify and analyze potential drug leads for AD treatment, ultimately suggesting a promising new inhibitor for further development.
Want 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!