Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

• Published in: Marine drugs Vol. 16; no. 3; p. 94
• Main Authors: Zhu, Yong-Zhe, Liu, Jing-Wen, Wang, Xue, Jeong, In-Hong, Ahn, Young-Joon, Zhang, Chuan-Jie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.03.2018; MDPI
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - metabolism; Animals; Anti-Infective Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Aquatic Organisms - chemistry; Aspartic Acid Endopeptidases - antagonists & inhibitors; BACE1; Bacteria - drug effects; Bio-assays; Bioactive compounds; bioassay-directed isolation; Bioassays; Biological Products - chemistry; Biological Products - pharmacology; Data processing; Disease resistance; Drug development; E coli; Enzymes; Ethanol; Fractionation; Humans; marine bioactive; Mass spectrometry; Mass spectroscopy; Medical treatment; Medicine; Minimum inhibitory concentration; NMR; Nuclear magnetic resonance; Polychaeta - chemistry; Salmonella; Steroids - chemistry; Steroids - pharmacology; Urechis unicinctus; β-Site APP-cleaving enzyme 1; BACE1; antimicrobial activity; Alzheimer’s disease; bioassay-directed isolation; Urechis unicinctus; marine bioactive
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md16030094

The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer's disease (AD). In this study, , which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4- -3-one, cholesta-4,6- -3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, ¹H, and C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4- -3-one showed significant inhibitory activity against BACE1 with EC values of 116.3 and 390.6 µM, respectively. Cholesta-4,6- -3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against , , , and , with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.