Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking.
Mar Drugs
; 20(9)2022 Aug 29.
Article
in En
| MEDLINE
| ID: mdl-36135743
ABSTRACT
Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. A total of 12 previously reported bromotyrosine-derived alkaloids were isolated from the marine sponge species Pseudoceratina durissima, and the compound, (+)-aeroplysinin-1 (1) displayed activity against the MRSA pathogen (MIC <32 µg/mL). The compounds (1−3, 6 and 9) were assessed for their central nervous system (CNS) interaction and behavioral toxicity to zebrafish (Danio rerio) larvae, whereby several of the compounds were shown to induce significant hyperactivity. Anthelmintic activity against the parasitic nematode Haemonchus contorutus was also evaluated (2−4, 6−8).
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Porifera
/
Biological Products
/
Alkaloids
/
Anthelmintics
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Animals
Language:
En
Journal:
Mar Drugs
Journal subject:
BIOLOGIA
/
FARMACOLOGIA
Year:
2022
Type:
Article
Affiliation country:
Australia