Using virtual AChE homology screening to identify small molecules with the ability to inhibit marine biofouling

Arabshahi, Homayon John (author), Trobec, Tomaž (author), Foulon, Valentin (author), Hellio, Claire (author), Frangež, Robert (author), Sepčić, Kristina (author), Cahill, Patrick (author), Svenson, Johan (author)

The search for effective yet environmentally friendly strategies to prevent marine biofouling is hampered by the large taxonomic diversity amongst fouling organisms and a lack of well-defined conserved molecular targets. The acetylcholinesterase enzyme catalyses the breakdown of the neurotransmitter acetylcholine, and several natural antifouling allelochemicals have been reported to display acetylcholinesterase inhibitory activity. Our study is focussed on establishing if acetylcholinesterase can be used as a well-defined molecular target to accelerate discovery and development of novel antifoulants via sequential high-throughput in silico screening, in vitro enzymatic studies of identified compound libraries, and in vivo assessment of the most promising lead compounds. Using this approach, we identified potent cholinesterase inhibitors with inhibitory concentrations down to 3 mM from a 10,000 compound library. The most potent inhibitors were screened against five microfouling marine bacteria and marine microalgae and the macrofouling tunicate Ciona savignyi. No activity was seen against the microfoulers but a potent novel inhibitor of tunicate settlement and metamorphosis was discovered. Although only one of the identified active cholinesterase inhibitors displayed antifouling activity suggesting the link between cholinesterase inhibition and antifouling is limited to certain compound classes, the study highlights how in silico screening employed regularly for drug discovery can also facilitate discovery of antifouling leads.

• Language: English
• Keywords: homology screening, in silico screening, in vitro enzymatic studies, cholinesterase, AChE inhibitor, antifouling
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Publication date: 13.12.2021
• Year: 2021
• Number of pages: 12 str.
• Numbering: Vol. 8, art. 762287
• PID: 20.500.12556/RUL-133797
• UDC: 636.09:575
• ISSN on article: 2296-7745
• DOI: 10.3389/fmars.2021.762287
• COBISS.SI-ID: 89164547
• Publication date in RUL: 15.12.2021

Record is a part of a journal

• Title: Frontiers in marine science
• Shortened title: Front. mar. sci.
• Publisher: Frontiers Media
• ISSN: 2296-7745
• COBISS.SI-ID: 523094809

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 15.12.2021