Marine pharmacology in 2003–4: Marine compounds with anthelmintic antibacterial, anticoagulant

29 Pages·2007·1.77 MB·English

ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
www.elsevier.com/locate/cbpc
–
Marine pharmacology in 2003 4: Marine compounds with anthelmintic
antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial,
antiplatelet, antiprotozoal, antituberculosis, and antiviral activities;
affecting the cardiovascular, immune and nervous systems,
and other miscellaneous mechanisms of action
⁎
Alejandro M.S. Mayera, , Abimael D. Rodríguezb, Roberto G.S. Berlinckc, Mark T. Hamannd
a DepartmentofPharmacology,ChicagoCollegeofOsteopathicMedicine,MidwesternUniversity,
55531stStreet,DownersGrove,Illinois60515,USA
bDepartmentofChemistry,UniversityofPuertoRico,SanJuan,PuertoRico00931,USA
c InstitutodeQuimicadeSaoCarlos,UniversidadedeSaoPaulo,SaoCarlos,13560-970,Brazil
d SchoolofPharmacy,TheUniversityofMississippi,FaserHall,University,Mississippi38677,USA
Received28October2006;receivedinrevisedform29January2007;accepted30January2007
Availableonline9February2007
Abstract
Thecurrentmarinepharmacologyreviewthatcoversthepeer-reviewedliteratureduring2003and2004isasequeltotheauthors'1998–2002
reviews,andhighlightsthepreclinicalpharmacologyof166marinechemicalsderivedfromadiversegroupofmarineanimals,algae,fungiand
bacteria.Anthelmintic,antibacterial,anticoagulant,antifungal,antimalarial,antiplatelet,antiprotozoal,antituberculosisorantiviralactivitieswere
reportedfor67marinechemicals.Additionally45marinecompoundswereshowntohavesignificanteffectsonthecardiovascular,immuneand
nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular
targetsandthusmaypotentiallycontributetoseveralpharmacologicalclasses.Thus,during2003–2004,researchonthepharmacologyofmarine
natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia,
Israel,Italy,Japan,Mexico,Morocco,theNetherlands,NewZealand,Norway,Panama,thePhilippines,Portugal,Russia,Slovenia,SouthKorea,
Spain,Thailand,Turkey,UnitedKingdom,andtheUnitedStates,contributednumerouschemicalleadsforthecontinuedglobalsearchfornovel
therapeutic agents with broadspectrum activity.
©2007Elsevier Inc.All rights reserved.
Keywords:Drug-leads;Marine;Metabolites;Naturalproducts;Pharmacology;Review;Toxicology
1. Introduction chemicalswhosestructureshavebeenestablishedareincludedin
the present review. As in our previous reviews, we have used
The purpose of this article is to review the 2003–4 primary Schmitz'schemicalclassification(Schmitzetal.,1993)toassign
literature on pharmacological studies with marine natural each marine compound to a major chemical class, namely,
products using the same format as in our previous reviews of polyketides, terpenes, nitrogen-containing compounds or poly-
the marine pharmacology peer-reviewed literature (Mayer and saccharides. Those publications reporting anthelmintic antibac-
Lehmann, 2000), (Mayer and Hamann, 2002, 2004, 2005). terial, anticoagulant, antifungal, antimalarial, antiplatelet,
Consistent with our previous reviews, only those articles antiprotozoal,antituberculosisorantiviralpropertiesof67marine
reporting on the bioactivity or pharmacology of 166 marine chemicalshavebeentabulatedinTable1withthecorresponding
structures shown in Fig. 1. The articles reporting on 45 marine
⁎ compounds affecting the cardiovascular, immune and nervous
Correspondingauthor.Tel.:[phone];fax:[phone].
E-mailaddress:[email protected](A.M.S.Mayer). systems, as well as those with anti-inflammatory effects are
1532-0456/$-seefrontmatter©2007ElsevierInc.Allrightsreserved.
doi:10.1016/j.cbpc.2007.01.015
554 A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
Table1
Marine pharmacology in 2003–4: marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal,
antituberculosis,andantiviralactivities
Drugclass Compound/organisma Chemistry Pharmacologicactivity MMOAb Countryc References
Anthelmintic Thiocyanatins(1–4)/sponge Polyketided Nematocidalactivityto Undetermined AUS (Caponetal.,2004b)
Haemonchuscontortus
Antibacterial KalihinolYandX(5,6)/ Diterpenee B.subtilisinhibition Folatebiosynthesis PHIL,USA (Bugnietal.,2004)
sponge inhibition
Antibacterial MC21A(7)/bacterium Bromophenol Methicillin-resistant Permeabilizationof JAPN (Isnansetyoetal.,2003)
S.aureusinhibition cellmembrane
comparabletovancomycin
Antibacterial NagelamideA(8)/sponge Alkaloidf M.luteus,B.subtilisand Proteinphosphatase AUS,JAPN (Endoetal.,2004)
E.coliinhibition 2Ainhibition
Antibacterial Plicatamide(9)/tunicate Peptidef Methicillin-resistant Bindtoplasma USA (Tincuetal.,2003)
S.aureus,L.monocytogenes, membranecausing
E.coliandP.aeruginosa K+effluxand
inhibition depolarization
Antibacterial Manoalide(10)/sponge Sesterterpenee S.aureusinhibition Undetermined JAPN (Namikoshietal.,2004)
Antibacterial MelophlinC(11)/sponge Polyketided B.subtilisandS.aureus Undetermined CHI,INDO, (Wangetal.,2003a)
inhibition GER,NETH
Antibacterial EudistominX(12)/tunicate Alkaloidf S.aureus,B.subtilisand Undetermined GER (Schuppetal.,2003)
E.coliinhibition
Antibacterial DolabellaninB2(13)/seahare Peptidef B.subtilis,H.influenzaand Undetermined JAPN (Iijimaetal.,2003)
V.vulnificusinhibition
Antibacterial PseudopterosinXandY Diterpenee S.aureus,S.pyogenes,and Undetermined CAN,USA (Ataetal.,2004)
(14,15)/softcoral E.faecalisinhibition
Antibacterial Sinularialipids(16–18)/ Polyketided B.subtilis,B.pumilus, Undetermined RUS (Dmitrenoketal.,2003)
softcoral E.coliandP.aeruginosa
inhibition
Antibacterial Rhodomela Bromophenold S.aureus,S.epidermidis Undetermined CHI (Xuetal.,2003)
bromophenol(19)/alga andP.aeruginosainhibition
Antibacterial Cribrostatin6(20)/sponge Alkaloidf S.pneumoniaeinhibition Undetermined USA (Pettitetal.,2004)
Antibacterial PurpuramineL(21)/sponge Bromotyrosine S.aureus,B.subtilisand Undetermined IND (Goudetal.,2003b)
alkaloidsf C.violaceuminhibition
Antibacterial Germacrane(22)/sponge Sesquiterpenee S.aureusandB.subtilis Undetermined THAI (Satitpatipanetal.,2004)
inhibition
Antibacterial Ptilocaulis Alkaloidf S.aureusinhibition Undetermined USA (Yangetal.,2003c)
guanidine(23)/sponge
Antibacterial MembranolidesCand Diterpenee S.aureusandE.coli Undetermined USA (Ankisettyetal.,2004)
D(24,25)/sponge inhibition
Antibacterial Arenicins1and2 Peptidef E.coli,L.monocytogenes Undetermined RUS (Ovchinnikovaetal.,
(26,27)/polychaeta andC.albicansinhibition 2004)
Antibacterial Perinerin(28)/ Peptidef Gram-negative,Gram- Undetermined CHI (Panetal.,2004)
polychaeta positiveandfungalinhibition
Antibacterial Hippoglossoidespeptide Peptidef P.aeruginosaandS.aureus Undetermined CAN (Patrzykatetal.,2003)
(29)/Americanplaice inhibition
Anticoagulant DysinosinC(30)/sponge Peptidef FactorVIIaandthrombin Twostructural AUS (Carrolletal.,2004)
inhibition motifscontributeto
proteasebinding
Anticoagulant Fucosylated Polysaccharideg Anticoagulant,bleeding Accelerated BRA (Zancanetal.,2004)
chondroitinsulfate andantithromboticeffects thrombininhibition
(31)/seacucumber invivo
Anticoagulant Sulfatedgalactans Polysaccharideg Antithrombin-mediated Interactionholds BRA (Meloetal.,2004)
(32,33)/algaandseaurchin anticoagulantactivity antithrombininactive
Antifungal Astroscleridaesterol Sterolsulfated S.cerevisiaeinhibition Undetermined USA (Yangetal.,2003b)
(34)/sponge
Antifungal Dysideaarenaria Terpenee Fluconazoleresistance MDR1-typeefflux USA (Jacobetal.,2003)
sterol(35)/sponge reversalinC.albicans pumpinhibition
Antifungal Massadine(36)/sponge Alkaloidf GeranylgeranyltransferaseI Undetermined JAPN,NETH (Nishimuraetal.,2003)
inhibition
Antifungal NaamineG(37)/sponge Alkaloidf C.herbaruminhibition Undetermined GER,NETH (Hassanetal.,2004)
Antifungal UtenosponginB(38)/sponge Diterpenee C.tropicalesand Undetermined NETH,MOR, (Rifaietal.,2004)
F.oxysporuminhibition PORT
Antifungal (2S,3R)-2-aminododecan-3-ol Polyketided C.albicansinhibition Undetermined BRA,USA (Kossugaetal.,2004)
(39)/ascidian
Antimalarial Bielschowskysin(40)/coral Diterpenee P.falciparuminhibition Undetermined PAN,USA (Marreroetal.,2004)
Antimalarial Briarellins(41–43)/coral Diterpenee P.falciparuminhibition Undetermined PAN,USA (Ospinaetal.,2003)
A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581 555
Table1(continued)
Drugclass Compound/organisma Chemistry Pharmacologicactivity MMOAb Countryc References
Antimalarial Cembradiene(44)/seawhip Diterpenee P.falciparuminhibition Undetermined PAN,USA (Weietal.,2004)
Antimalarial Dolastatin10(45)/seahare Peptidef P.falciparumFCH5.C2 Microtubuleand USA (Fennelletal.,2003)
inhibition mitoticinhibition
Antimalarial ManzamineA(46)/sponge Alkaloidf P.falciparumD6andW2 Undetermined USA (Raoetal.,2003)
inhibition
Antimalarial TrioxacarcinAandD Glycosided,g P.falciparumstrainsNF54 Undetermined NETH,GER (Maskeyetal.,2004)
(48,49)/bacterium andK1inhibition
Antiprotozoal RenieramycinA(50)/sponge Alkaloidf Leishmaniaamazonensis Undetermined JAPN (Nakaoetal.,2004a)
inhibition
Antiprotozoal EuplotinC(51)/ciliate Sesquiterpenee Leishmaniamajor Undetermined ITA (Savoiaetal.,2004)
andinfantuminhibition
Antiprotozoal Defensins/mussel Peptidef T.bruceiandL.major Undetermined BEL,FRA (Rochetal.,2004)
inhibition
Antituberculosis (+)-8-hydroxymanzamineA Alkaloidf M.tuberculosisinhibition Undetermined USA (Raoetal.,2003)
(47)/sponge
Antituberculosis Homopseudopteroxazole Diterpenee M.tuberculosisinhibition Undetermined USA (Rodríguezetal.,2003)
(52)/softcoral
Antituberculosis IngenamineG(53)/sponge Alkaloidf S.aureus,E.coliand Undetermined BRA,GER (DeOliveiraetal.,2004)
resistantS.aureusinhibition
Antituberculosis 12-Deacetoscalarin Sesterterpenee M.tuberculosisinhibition Undetermined THAI (Wonganuchitmetaetal.,
19-acetate(54)/sponge 2004)
Antituberculosis Oceanapisidesp.compounds Polyketided Mycothiol-S-conjugate Non-competitive USA (Nicholasetal.,2003)
(55–57)/sponge amidaseinhibition inhibition
Antiplatelet XetosponginA(58)/sponge Alkaloidf Collagen-inducedplatelet Undetermined PHIL,USA (Pimenteletal.,2003)
aggregationinhibition
Antiplatelet Zoanthaminealkaloids Alkaloidf Agonist-inducedplatelet Undetermined BRA,SPA (Villaretal.,2003)
(59–60)/zoanthids aggregationinhibition
Antiviral Crambescidin826 Alkaloidf HIV-1envelope-mediated Undetermined USA (Changetal.,2003)
(61)/sponge fusioninhibitioninvitro
Antiviral Dehydrofurodendin Furanoterpenee ReversetranscriptaseRNA- Undetermined ISRA,FRA (Chilletal.,2004)
(62)/sponge andDNA-directedDNA
polymeraseinhibition
Antiviral NeamphamideA(63)/sponge Depsipeptidef HIV-growthinhibition Undetermined USA (Okuetal.,2004)
Antiviral Dictyotaditerpenes Diterpenee InhibitionofHIV-1 RNA-dependent BRA (Pereiraetal.,2004)
(64,65)/alga replicationincellline DNA-polymerase
RTinhibition
Antiviral Petrosins(66,67)/sponge Alkaloidf HIV-growthinhibition Giantcellformation IND (Goudetal.,2003a)
andRTinhibition
a Organism,KingdomAnimalia:flounder(Americanplaice)andtunicates(PhylumChordata);polychaeta(PhylumAnnelida);seaurchinsandcucumbers(Phylum
Echinodermata),musselsandseahares(PhylumMollusca),sponges(PhylumPorifera);corals,seawhipsandzoanthids(PhylumCnidaria);KingdomMonera:bacteria
(PhylumCyanobacteria);KingdomPlantae:algae;KingdomProtista:ciliates(PhylumCiliophora).
b MMOA:molecularmechanismofaction.
c Country:AUS:Australia;BEL:Belgium;BRA:Brazil;CAN:Canada;CHI:China;FRA:France;GER:Germany;IND:India;INDO:Indonesia;ISRA:Israel;
ITA:Italy;JAPN:Japan;MOR:Morocco;NETH:TheNetherlands;NOR:Norway;PAN:Panama;PHIL:ThePhillipines;PORT:Portugal;RUS:Russia;SPA:Spain;
THAI:Thailand.
d Polyketide.
e Terpene.
f Nitrogen-containingcompound.
g Polysaccharide.
groupedinTable2andthestructurespresentedinFig.2.Finally Botryocladialeptopoda (Lakshmi et al., 2004); antiviral effects
54marinecompoundstargetinganumberofdistinctcellularand of a sulfated exopolysaccharide from the marine microalga
moleculartargetsandmechanismsareshowninTable3andtheir Gyrodinium impudicum (Yim et al., 2004) and Sargassuum
structures depicted in Fig. 3. Publications on the biological or patens (Zhu et al., 2004); a polyhydroxylated fucophlorethol
pharmacologicalactivityofmarineextractsorasyetstructurally isolated from the marine brown alga Fucus vesiculosus
uncharacterizedmarinecompoundshavebeenexcludedfromthe shown to be bactericidal towards selected Gram-positive and
present review, although several promising reports were pub- Gram-negative bacteria in vitro (Sandsdalen et al., 2003); and
lished during 2003–4: a specific inhibitor of a thyrotropin an improvement of “current cytokine-based therapies”
releasing hormone-specific peptidase (Pascual et al., 2004); by sulphated polysaccharides purified from the green alga
antimicrobial activity in sub-Arctic marine invertebrates Codium fragile, as well as fucoidan and carrageenan, isolated
(Lippert et al., 2003); antifilarial activity of the red alga from brown and red algae, respectively (Nika et al., 2003).
556 A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
2. Marine compounds with anthelminthic, antibacterial, 2.1. Anthelminthic and antibacterial compounds
anticoagulant, antifungal, antimalarial, antiplatelet,
antiprotozoal, antituberculosis, and antiviral activities One study contributed to the search of novel anthelmintic
marine natural products during 2003–4. The novel acyclic
Table1summarizesnew pharmacologicalfindings reported lipids thiocyanatins (1–4), were isolated from the Australian
during 2003–4 on the preclinical anthelminthic, antibacterial, spongeOceanapiasp.(Caponetal.,2004b)andwereshownto
anticoagulant, antifungal, antimalarial, antiplatelet, antiproto- be nematocidal (LD =3.1–8.3 μg/mL) to the commercial
99
zoal, antituberculosis, and antiviral pharmacology of the 67 livestock parasite Haemonchus contortus. Although the mech-
marine naturalproductsshown inFig. 1. anismofactionofthesecompoundsremainsundetermined,the
Fig.1.
A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581 557
Fig.1(continued).
investigatorsnotedthatboththe2°-alcohol,SCNfunctionalities pyranyl-type kalihinols Y (5) and X (6), although potent
and chain length influenced thenematocidal activity. antibacterials (MIC=1.56 μg/mL), were however less selective
Inviewofthefactthatresistancetocurrentantibioticsremainsa inhibitors of bacterial folate biosynthesis than the furanyl type
significant challenge for pathogenic bacterial infections, during kalihinols, with the “C-10 position important for potency”.
2003–4,19studiescontributedtothesearchfornovelantibacterial Isnansetyo and Kamei (2003) reported that a bactericidal
marinenaturalproducts,anincreasefrom1998–2002(Mayerand compound named MC21-A (7), a 3,3′,5,5′-tetrabromo-2,2′-
Lehmann, 2000; Mayer and Hamann, 2002, 2004, 2005). Four biphenyldiol,fromthenewmarinebacteriumPseudoalteromonas
studies reported on the mechanism of action of novel marine phenolicasp.nov.MC21-Awasbactericidal(MIC=1–2μg/mL)
antibacterialagents(2–6;Fig.1).Bugnietal.(2004)investigateda against10clinicalisolatesofmethicillin-resistantStaphylococcus
seriesofkalihinols,diterpenesisolatedfromthePhilippinemarine aureus, and displayed comparable bioactivity to vancomycin
sponge Acanthella cavernosa, as potential bacterial folate (MIC=0.25–2 μg/mL). The mechanism of action of MC21-A
biosynthesis inhibitors. The investigators reported that the involvedpermeabilizingbacterialcellmembranes,andthus“might
558 A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
Fig.1(continued).
be a useful compound” because of a mode of action that differs extensive and detailed mechanistic study these investigators
from vancomycin. A new dimeric bromopyrrole alkaloid, discoveredthatdespiteitssmallsize,theoctapeptideplicatamide
nagelamideG(8)wasisolatedfromtheOkinawanmarinesponge proved to be a potent, rapidly acting and broad spectrum
Agelas sp. (Endo et al., 2004). Nagelamide G exhibited antimicrobial.Thefactthatbothwildtypeandmethicilin-resistant
antibacterialactivityagainstM.luteus,B.subtilisandE.coli,but S. aureus responded to plicatamide with a massive and rapid
weakly inhibited protein phosphatase 2 A (IC =13 μM), thus potassium efflux is “consistent with an antimicrobial mechanism
50
suggestingthatthisenzymemaynotbethemainmoleculartarget thattargetstheircellmembrane”.
responsible for theantibacterial activity of this compound.Tincu Although additional novel marine antibacterials were
etal.(2003)reportedanewantimicrobialoctapeptideplicatamide reported in 2003–4, no mechanism of action studies were
(9)fromthehemocytesofthemarinetunicateStyelaplicata.Inan reported for compounds (10–29). Nevertheless, these studies
A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581 559
Fig.1(continued).
highlight the fact that novel antibiotics are present in marine antibacterial activity” against B. subtilis and S. aureus. One
bacteria,tunicates,seahares,softcorals,algae,sponges,worms, paper reported on new antimicrobial compounds isolated
and fish. Two papers reported on antibacterial activity in from marine tunicates: Schupp et al. (2003) discovered that
compounds isolated from marine sponges: Namikoshi et al. the β-carboline eudistomin X(12), isolated from the Microne-
(2004) reported the isolation of several manoalide derivatives sian ascidian Eudistoma sp. was active against B. subtilis,
(10) from a Luffariella sp. sponge collected in Palau, which S.aureusandE.coli.Onepaperreportedonanewantimicrobial
wereactiveagainstS.aureusat5–10μg/disk.Theinvestigators peptide isolated from sea hares: Iijima et al. (2003) reported a
noted that the presence of an “OH group at the C-25 position novel33aminoacidantimicrobialpeptidedolabellaninB2(13)
(hemiacetal moiety) is important for antibacterial activity.” from the sea hare Dolabella auricularia. One hundred percent
Wang et al. (2003a) reported thirteen novel tetramic acids inhibition of growth of B. subtilis, H. influenza and Vibrio
isolated from the marine sponge Melophlus sarassinorum. vulnificus was reported with 2.5–5 μg/mL dolabellanin B2.
Interestingly, only melophlin C (11) displayed “pronounced Two papers reported on new antimicrobial peptides isolated
560 A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
Fig.1(continued).
from marine soft corals: Ata et al. (2004) reported two new the MIC were not reported, “preliminary tests for antibacterial
diterpenes,pseudopterosinXandY(14–15)fromthesoftcoral activityoflipids”demonstratedthatthesecompoundsinhibited
Pseudopterogorgia elisabethae which showed antibacterial thegrowthofE.coli,Pseudomonasaeruginosa,B.subtilisand
activityagainstGram-positivebacteriaStreptococcuspyogenes, B.pumilusonsolidagar.Onepaperreportedonthepresenceof
S. aureus, and Enterococcus faecalis, while being inactive antibacterial compounds in marine algae: Xu et al. (2003)
against Gram-negative bacteria. Dmitrenok et al. (2003) reported that among 5 bromophenols isolated from the marine
reported several sphingolipids and glycolipids (16–18) from red alga Rhodomela confervoides, the known compound bis
soft corals of the Andaman Islands (Indian Ocean). Although (2,3-dibromo-4,5-dihydroxybenzyl) ether (19) showed
A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581 561
Table2
Marinepharmacologyin2003–4:marinecompoundswithanti-inflammatoryactivity,andaffectingthecardiovascular,immuneandnervoussystems
Drugclass Compound/organisma Chemistry Pharmacologicalactivity MMOAb Countryc References
Anti-inflammatory Astaxanthin(68)/salmon, Tetraterpened Inhibitionofendotoxin- iNOS,NO,TNF-α JAPN (Ohgamietal.,2003)
seastars induceduveitisinrats andPGE inhibition
2
Anti-inflammatory Bolinaquinone(69)/ Merosesquiterpened Inhibitionofcytokine, sPLA inhibition SPA,ITA (Lucasetal.,2003b)
2
sponge iNOSandeicosanoids
Anti-inflammatory CacospongionolideB Sesterterpened Nitricoxide,PGE and Nuclearfactor-κB SPA,ITA (Posadasetal.,2003a)
2
(70)/sponge TNF-αinhibitionin inhibition
vitroandinvivo
Anti-inflammatory ClathriolB(71)/sponge Sterold Neutrophilsuperoxide Undetermined NZEL (Keyzersetal.,2003)
inhibition
Anti-inflammatory Conicamin(72)/tunicate Indolealkaloide Histamineantagonist Undetermined ITA (Aielloetal.,2003)
Anti-inflammatory Cycloamphilectene2 Diterpened Nitricoxideinhibition InhibitionofNF-κB ITA,SPA (Lucasetal.,2003a)
(73)/sponge pathway
Anti-inflammatory PlakohypaphorineD Indolealkaloide Histamineantagonist Undetermined ITA (Borrellietal.,2004)
(74)/sponge
Anti-inflammatory PourewicacidAand Diterpenesd Superoxideinhibition Undetermined NZEL (Keyzersetal.,2004)
methylpourewateB
(75,76)/sponge
Anti-inflammatory CadlinolideC(77)/sponge Diterpened Superoxideinhibition Undetermined NZEL (Keyzersetal.,2004)
Anti-inflammatory PetrocortyneA(78)/sponge Polyacetyleneg Macrophage NOandTNF-α SKOR (Hongetal.,2003)
inflammatory inhibition
mediatorinhibition
Anti-inflammatory PetrosaspongiolideM Sesterterpened Nitricoxide,PGE and Nuclearfactor-κB ITA,SPA (Posadasetal.,2003b)
2
(79)/sponge TNF-αinhibitionin inhibition
vitroandinvivo
Anti-inflammatory PetrosaspongiolidesM-R Sesterterpenesd Macrophage PLA inhibition ITA (Montietal.,2004)
2
(79–83)/sponge inflammatorymediator
inhibition
Anti-inflammatory PseudopterosinN Diterpened Inhibitionofmouseear Undetermined USA (Ataetal.,2003)
(84)/seawhip inflammation
Anti-inflammatory Seco-pseudopterosinE Diterpened Inhibitionofmouseear Undetermined USA (Ataetal.,2003)
(85)/seawhip inflammation
Anti-inflammatory Elisabethadione(86)/ Diterpened Inhibitionofmouseear Undetermined USA (Ataetal.,2003)
seawhip inflammation
Anti-inflammatory PseudopterosinR Diterpened Microgliathromboxane Undetermined USA (Rodríguezetal.,2004)
(87)/seawhip B inhibition
2
Cardiovascular CallipeltinA(88)/sponge Depsipeptidee Affectedrestingaorta Na+-ionophore ITA (Trevisietal.,2004)
contraction action
Immunesystem Codiumfragile Polysaccharidef BindingtoIL-2,IL-7 Undetermined UK (Nikaetal.,2003)
polysaccharide/alga andINF-γ
Immunesystem Sulfircin(89)/sponge Sesterterpened MobilizationofTcells CCR7chemokine USA (Yangetal.,2003d)
anddendriticcells receptorbinding
Immunesystem Mucins/seastar Polysaccharidef Inhibitionofneutrophil Undetermined UK (Bavingtonetal.,2004)
adhesion
Immunesystem PerybysinsA–D Sesquiterpenesd Inhibitionofhuman Undetermined JAPN (Yamadaetal.,2004)
(90–93)/fungus leukemiacelladhesion
Immunesystem Phycarine/alga Polysaccharidef Stimulationof IL-1,IL-6and FRA,USA (Vetvickaetal.,2004)
macrophagephagocytosis TNF-αsynthesis
Immunesystem SulfatedPMG(94)/alga Polysaccharidef InhibitionofHIVvirus BindingtoCD4 CHI (Meiyuetal.,2003)
infectionoflymphocytes receptoron
lymphocytes
Immunesystem SulfatedPMG(94)/alga Polysaccharidef Bindingtolymphocytes Interactionwith CHI (Miaoetal.,2004)
CD4receptor
Nervoussystem Petrosaspongiolide Sesterterpened Reductionofmorphine Undetermined ITA (Capassoetal.,2003)
M(79)/sponge withdrawalinvitro
Nervoussystem Aplidine(95)/tunicate Depsipeptidee Inhibitionofaggregation Undetermined SPA,USA (Perezetal.,2003)
ofprionpetideinto
β-sheetfibrils
Nervoussystem AspermytinA(96)/fungus Polyketideg Inductionofneurite Undetermined JAPN (Tsukamotoetal.,
outgrowth 2004a)
Nervoussystem LabuanineA(97)/sponge Pyridoacridine Inductionofneuite Undetermined JAPN,INDO (Aokietal.,2003)
alkaloide outgrowth
Nervoussystem LinckosidesC–E Steroidal Inductionofneurite Undetermined JAPN (Qietal.,2004)
(98–100)/seastar glycosided outgrowth
(continuedonnextpage)
562 A.M.S.Mayeretal./ComparativeBiochemistryandPhysiology,PartC145(2007)553–581
Table2(continued)
Drugclass Compound/organisma Chemistry Pharmacologicalactivity MMOAb Countryc References
Nervoussystem Parguerol-isoparguerol Diterpened Inductionofneurite Undetermined JAPN (Tsukamotoetal.,
(101–102)/seahare outgrowth 2004b)
Nervoussystem Sargaquinoicacid Meroditerpened Inductionofneurite PI-3kinase JAPN (Tsangetal.,2004;
(103)/alga outgrowth independent; Kameietal.,2003)
TrKA-MAPkinase
andadenylate
cyclase-PKA
dependent
Nervoussystem SJG-2ganglioside Ganglioside Inductionofneurite Undetermined JAPN (Kanekoetal.,2003)
(104)/seacucumber outgrowth
Nervoussystem Cribronicacid Aminoacide Convulsantactivity Bindingto JAPN (Sakaietal.,2003)
(105)/sponge inmice NMDA-type
receptor
Nervoussystem DysibetaineCPa–CPb Betaine Bindingtoionotropic Undetermined JAPN (Sakaietal.,2004)
(106,107)/sponge glutamatereceptors
Nervoussystem JamaicamideA Lipopeptidee Sodiumchannelblocking Undetermined USA (Edwardsetal.,2004)
(108)/cyanobacterium
Nervoussystem Esmodil(109)/sponge Quaternaryamine Acetylcholinemimetic Undetermined AUS (Caponetal.,2004a)
Nervoussystem ω-conopeptideMVIIA Peptidee Inhibitionofrefractory BindingtoN-type USA (Staatsetal.,2004)
(110)/snail paininpatientswith Ca2+channels
AIDSorCancer
Nervoussystem δ-conotoxin(111)/snail Peptidee Na+currentinhibition Undetermined IND (Sudarslaletal.,2003)
Nervoussystem χ-conopeptide Peptidee Norepinephrine Non-competitive AUS (Sharpeetal.,2003)
MrIA(112)/snail transporterinhibition bindingatthe
antidepressant
bindingsite
Nervoussystem Acidicoligosaccharide/alga Polysaccharidef Inhibitionofamyloid Inhibitionof CHI (Huetal.,2004)
betatoxicity apoptosisand
intracellularCa2+
a Organism:KingdomAnimalia:seawhip(PhylumCnidaria);tunicate(PhylumChordata),seastarandcucumber(PhylumEchinodermata);seahareandsnail
(PhylumMollusca);sponge(PhylumPorifera);KingdomFungi:fungus;KingdomPlantae:alga;KingdomMonera:bacterium(PhylumCyanobacteria).
b MMOA:molecularmechanismofaction,NO:nitricoxide.
c Country:AUS:Australia;CHI:China;FRA:France;INDO:Indonesia;ITA:Italy;JAPN:Japan;N.ZEL:NewZealand;SPA:Spain;S.KOR:SouthKorea;UK:
UnitedKingdom.
d Terpene.
e Nitrogen-containingcompound.
f Polysaccharide.
g Polyketide.
antibacterial activity against S. aureus (MIC=70 μg/mL), Sta- 25)derivedfromanAntarcticcactussponge,displayed“modest
phylococcusepidermidisandP.aeruginosa(MIC=70μg/mL). yet broad spectrum” Gram-negative antibiotic activity (Anki-
Additional antibacterial marine natural products were isolated settyetal.,2004).Twonovelantibacterialpeptideswereisolated
from sponges: Pettit et al. (2004) reported the antibacterial from marine worms: Ovchinnikova et al. (2004) purified and
activityofanovelnitrogenheterocycliccompoundcribrostatin characterized two small 21-residue peptides arenicin-1 and-2
6 (20) isolated from the dark-blue marine Cribochalina sp. (26–27), from the coelomocytes of the marine lugworm Areni-
sponge. Cribrostatin 6 showed antibacterial activity against colamarina.BotharenicinswereactiveagainstGram-positiveL.
Gram-positive bacteria, and it was most active against monocytogenes, Gram-negative E. coli and the fungus
S.pneumoniae(MIC=0.5μg/mL),aleadingcauseofinfection C. albicans. Pan et al. (2004) isolated and characterized a 51-
andmortality worldwide. Goudetal.(2003b) reported anovel aminoacidhighlybasicandhydrophobicpeptideperinerin(28),
purpuramine L (21) from the Indian marine sponge Psamma- fromthemarineclamwormPerinereisaibuhitensis,anorganism
plysillapurpureawhichwasactiveagainstS.aureus,B.subtilis that is extensively used as bait in fisheries and aquaculture.
and C. violaceum. A new nitrogenous sesquiterpene germa- Perinerin, a peptide that is constitutively present in the marine
crane (22) was isolated from an Axinyssa n. sp. sponge that wormandwhosesequenceappearstobenovelamongallknow
demonstrated strong antimicrobial activity against S. aureus antimicrobial peptides, was active against Gram-negative and
and B. subtilis (Satitpatipan and Suwanborirux, 2004). Yang Gram-positive bacteria as well as fungi. Patrzykat et al. (2003)
et al. (2003c) isolated a new bicyclic guanidine alkaloid (23) reported active novel antimicrobials peptides by screening both
from the marine sponge Ptilocaulis spiculifer, contributing a genomic and mRNA transcripts from a number of different
new member to the crambescin A class of compounds. speciesofflatfish.ThemostactivepeptidecodedasNRC-13(29)
Interestingly, 50 μg of the guanidine alkaloid was as potent as which was derived from the American plaice Hippoglossoides
10μggentamicin.TwoditerpenesmembranolidesCandD(24, platessoides Frabricius, “rapidly (5 to 10 min) and efficiently