FN Archimer Export Format
PT J
TI Using Virtual AChE Homology Screening to Identify Small Molecules With the Ability to Inhibit Marine Biofouling
BT 
AF Arabshahi, Homayon John
   Trobec, Tomaž
   Foulon, Valentin
   Hellio, Claire
   Frangež, Robert
   Sepčić, Kristina
   Cahill, Patrick
   Svenson, Johan
AS 1:1;2:2;3:3;4:3;5:2;6:4;7:5;8:5;
FF 1:;2:;3:;4:;5:;6:;7:;8:;
C1 School of Chemistry, University of Auckland, Auckland, New Zealand
   Veterinary Faculty, Institute of Preclinical Sciences, University of Ljubljana, Ljubljana, Slovenia
   Laboratoire des Sciences de l’Environnement Marin (LEMAR) CNRS, IRD, Ifremer, Université de Bretagne Occidentale, Plouzané, France
   Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
   Cawthron Institute, Nelson, New Zealand
C2 UNIV AUCKLAND, NEW ZEALAND
   UNIV LJUBLJANA, SLOVENIA
   CNRS, FRANCE
   UNIV LJUBLJANA, SLOVENIA
   INST CAWTHRON, NEW ZEALAND
UM LEMAR
IN WOS Cotutelle UMR
   DOAJ
   copubli-europe
   copubli-int-hors-europe
IF 5.247
TC 5
UR https://archimer.ifremer.fr/doc/00740/85210/90222.pdf
LA English
DT Article
DE ;homology screening;in silico screening;in vitro enzymatic studies;cholinesterase;AChE inhibitor;antifouling
AB 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 μM 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. 
PY 2021
PD DEC
SO Frontiers In Marine Science
SN 2296-7745
PU Frontiers Media SA
VL 8
UT 000735952700001
DI 10.3389/fmars.2021.762287
ID 85210
ER

EF