title: Potent Antifouling Marine Dihydroquinolin-2(1H)-one-Containing Alkaloids from the Gorgonian Coral-Derived Fungus Scopulariopsis sp.
abstract: Marine biofouling has a major economic impact, especially when it occurs on ship hulls or aquaculture facilities. Since the International Maritime Organization (IMO) treaty to ban the application of organotin-based paints to ships went into effect in 2008, there is an urgent demand for the development of efficient and environmentally friendly antifouling agents. Marine microorganisms have proved to be a potential source of antifouling natural compounds. In this study, six dihydroquinolin-2-one-containing alkaloids, three monoterpenoids combined with a 4-phenyl-3,4-dihydroquinolin-2(1H)-one (1-3) and three 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloids (4-6), were isolated from the gorgonian coral-derived fungus Scopulariopsis sp. collected in the South China Sea. These dihydroquinolin-2-one-containing alkaloids were evaluated against the larval settlement of barnacle Balanus amphitrite, and antifouling activity was detected for the first time for this class of metabolites. All of them except 6 showed strong antifouling activity. Compounds 1 and 2 were discovered to be the most promising non-toxic antilarval settlement candidates. Especially, compound 1 is the strongest antifouling compound in nature until now which showed highly potent activity with picomolar level (EC50 17.5 pM) and a very safety and high therapeutic ratio (LC50/EC50 1200). This represents an effective non-toxic, anti-larval settlement structural class of promising antifouling lead compound.
authors.affiliation: Key Laboratory of Marine Drugs, The Ministry Education of China, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, People's Republic of China, shaochanglun@163.com.
authors.forename: Chang-Lun
authors.initials: CL
authors.lastname: Shao
authors.forename: Ru-Fang
authors.initials: RF
authors.lastname: Xu
authors.forename: Chang-Yun
authors.initials: CY
authors.lastname: Wang
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
authors.forename: Kai-Ling
authors.initials: KL
authors.lastname: Wang
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Wei
mesh_terms: D000470:Alkaloids / Q000032:analysis / Q000302:isolation & purification*; D000818:Animals; D037421:Anthozoa / Q000382:microbiology*; D001419:Bacteria / Q000187:drug effects; D001483:Base Sequence; D057219:Biofouling / Q000517:prevention & control*; D018929:Cell Culture Techniques / Q000379:methods; D002681:China; D017931:DNA Primers / Q000235:genetics; D020128:Inhibitory Concentration 50; D007814:Larva / Q000187:drug effects; D007928:Lethal Dose 50; D008969:Molecular Sequence Data; D009792:Oceans and Seas; D015363:Quinolones / Q000032:analysis / Q000302:isolation & purification*; D060645:Scopulariopsis / Q000737:chemistry* / Q000235:genetics; D017422:Sequence Analysis, DNA; D001468:Thoracica / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D017931:DNA Primers; D015363:Quinolones; C588100:dihydroquinolin-2(1H)-one
references.citation: Mar Biotechnol (NY). 2013 Aug;15(4):375-98
references.pmid: 23525893
references.citation: Prog Drug Res. 2001;56:121-54
references.pmid: 11417112
references.citation: J Nat Prod. 2011 Apr 25;74(4):629-33
references.pmid: 21348465
references.citation: Sci Total Environ. 2002 Jul 3;293(1-3):117-27
references.pmid: 12109466
references.citation: Mar Biotechnol (NY). 2006 Nov-Dec;8(6):634-40
references.pmid: 16924374
references.citation: Planta Med. 1982 May;45(5):31-4
references.pmid: 17396775
references.citation: J Nat Prod. 2013 Apr 26;76(4):779-82
references.pmid: 23586849
references.citation: J Chromatogr A. 2002 Sep 13;970(1-2):183-90
references.pmid: 12350092
references.citation: Lett Appl Microbiol. 2006 Oct;43(4):410-6
references.pmid: 16965372
references.citation: Nat Prod Rep. 2014 Jan 17;31(2):160-258
references.pmid: 24389707
references.citation: J Nat Prod. 2012 Mar 23;75(3):464-72
references.pmid: 22295903
references.citation: Nat Prod Rep. 2011 Feb;28(2):400-10
references.pmid: 21082120
references.citation: J Nat Prod. 2012 Mar 23;75(3):311-35
references.pmid: 22316239
references.citation: Cancer Res. 1988 Sep 1;48(17):4827-33
references.pmid: 3409223
references.citation: Biofouling. 2010;26(2):223-34
references.pmid: 19960389
references.citation: Biofouling. 2003 Aug;19(4):269-78
references.pmid: 14626846
references.citation: J Med Chem. 1999 Feb 11;42(3):393-9
references.pmid: 9986709
references.citation: Nat Commun. 2011;2:244
references.pmid: 21427715
references.citation: Nat Prod Rep. 2004 Feb;21(1):94-104
references.pmid: 15039837
references.citation: Crit Rev Toxicol. 1999 Jul;29(4):367-437
references.pmid: 10451264
references.citation: J Nat Prod. 2013 Oct 25;76(10):1896-901
references.pmid: 24099304
references.citation: Mar Biotechnol (NY). 1999 Sep;1(5):427-0436
references.pmid: 10525677
references.citation: Mar Biotechnol (NY). 2013 Oct;15(5):552-8
references.pmid: 23613141
references.citation: Nat Protoc. 2008;3(9):1494-500
references.pmid: 18772877
references.citation: Planta Med. 1993 Jun;59(3):250-2
references.pmid: 8316592
references.citation: Biofouling. 2011 Jan;27(1):87-98
references.pmid: 21161774
references.citation: Mol Ecol. 1993 Apr;2(2):113-8
references.pmid: 8180733
references.citation: Environ Sci Pollut Res Int. 2000;7(2):105-14
references.pmid: 19009431
references.citation: Arch Environ Contam Toxicol. 2007 Aug;53(2):227-32
references.pmid: 17549541