20.500.12556/RUL-133797 Using virtual AChE homology screening to identify small molecules with the ability to inhibit marine biofouling 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. homology screening in silico screening in vitro enzymatic studies cholinesterase AChE inhibitor antifouling true false true Angleški jezik Ni določen Članek v reviji 2021-12-15 13:43:36 2021-12-15 13:43:37 2022-09-13 03:52:42 0000-00-00 00:00:00 2021 0 0 12 str. art. 762287 Vol. 8 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2021-12-13 636.09:575 2296-7745 10.3389/fmars.2021.762287 89164547 RAZ_Arabshahi_Homayon_John_2021.pdf RAZ_Arabshahi_Homayon_John_2021.pdf 1 8AEFD939B41784005C58CFB072C44B7C c8a63288a6c16b6a0a714bb75e281529e71737bc64fc9b02058d4fed45cd12f6 77b0a29f-5da6-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152145 https://www.frontiersin.org/articles/10.3389/fmars.2021.762287/full 1 7fa725ba-5da4-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152144 Veterinarska fakulteta Biotehniška fakulteta 0 0 0