Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking
- Lever, J., Kreuder, F., Henry, J., Hung, A., Allard, P.M., Brkljača, R., Rix, C., Taki, A.C., Gasser, R.B., Kaslin, J., Wlodkowic, D., Wolfender, J.L., Urban, S.
- Marine drugs 20(9): (Journal)
- Registered Authors
- Kaslin, Jan
- MRSA pathogen, chemical space topology, cheminformatic analysis, in silico molecular docking, molecular networking, sponge metabolites, targeted anti-biotic isolation, virtual screening, zebrafish
- MeSH Terms
- Anti-Bacterial Agents/chemistry
- Anti-Bacterial Agents/pharmacology
- Biological Products*
- Molecular Structure
- 36135743 Full text @ Mar. Drugs
Lever, J., Kreuder, F., Henry, J., Hung, A., Allard, P.M., Brkljača, R., Rix, C., Taki, A.C., Gasser, R.B., Kaslin, J., Wlodkowic, D., Wolfender, J.L., Urban, S. (2022) Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking. Marine drugs. 20(9).
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).
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes