Investigation of the chemistry and antiparasitic activity of metabolites from Tasmanian marine organisms

More than 400 marine macroorganisms were collected from around the eastern and south eastern coasts of Tasmania. Organic extracts of these organisms were tested for activity against endo- and ecto-parasites of domestic animals. The incidence of high nematocidal activity was greatest for extracts of bryozoans (29%), a previously unrecognised source of nematocides. Ectoparasites were susceptible to about 10% of the extracts from each class of marine organism. The brown algae Sporochnus moorei and Perithalia caudata contained a nematocidal diprenylated phenol [3.8], LD99 50 jig/mi.-S. stylosus extract, lacking antiparasitic activity, contained a novel triprenylated phenol [3.13] and the related chromene [3.14]. A further triprenylated phenol [3.17] was detected. The brown alga Caulocystis cephalornithos contained 6-alkylsalicylic acids [3.19] - [3.23], known from other sources, which had nematocidal activity but could not account for the nematocidal activity of crude extracts. Labile precursors of the 6- alkylsalicylic acids were proposed as the major bioactive metabolites. The alga contained a unique profile of acetogenins which varied seasonally and between and within collection sites. The unreported enones [3.42] - [3.45] were present. Nematocidal and insecticidal activity of extracts from the red algae Jeannerettia lobata, Lophurella periclados and Polysiphonia nigrita was due to bromophenols. The most potent nematocide was 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol [3.60], LD99 <12.5 1.1g/ml. A Lissoclinum sp. ascidian contained varacin [4.1] and varacin A [4.2] which were lethal in the nematode assay via an indirect antibacterial action. The major pyridoacridines from the ascidian, shermilamine B [4.8], kuanoniarnine D [4.9] and stylesamine B [4.10] had modest nematocidal activity. Two novel pyridoacridines, proposed to be [4.11] and [4.12], were isolated from this ascidian. A Didemnum sp. ascidian contained three known [4.39] ‚ÄövÑvÆ [4.41] and one undescribed [4.42] aplysinopsins, not previously isolated from an ascidian, that were inactive in the antiparasitic assays. The extract of a Leptoclinides sp. ascidian had insecticidal and acaricidal activity. Glycosphingolipids [4.45], purines (including adenine) and nucleosides (including 2'-deoxyadenosine) present in the extract could not account for the antiparasitic activity. The bryozoan Amathia wilsoni contained the known amathamides A [5.1] and B [5.2] together with the closely related but not previously described (2S)-1-methyl-N[2-(2,4-dibromo-5-methoxyphenypethy1]-2-pyrrolidinecarboxamide [5.3]. Amathamide A had potent nematocidal activity (LD99 2.5 Kg/m1). Novel potent nematocides convolutamine H [5.5] and convolutindole A [5.6] were isolated from Amathia convoluta, with LD99 0.20 and 0.39 1.1g/m1 respectively. This bryozoan also contained a novel amathamide, proposed to exist as two amide rotamers [5.8a] and [5.8b], and a formamide of this amathamide [5.12]. A minor constituent was N-methyl-2[2,4-dibromo-5-methoxy]-ethanamine [5.10]. Nematocidal activity from a catenicellid bryozoan was associated with high levels of pavettine [5.73] and not with harman [5.70]. Homarine [5.79] from Ste ginoporella truncata lacked antiparasitic activity. A sponge contained the known nematocides, furodysin [6.2], furodysinin [6.3] and related metabolites [6.4] ‚ÄövÑvÆ [6.11], some of which are undescribed, as well as the putative precursor of these compounds, dehydrodendrolasin [6.1]. Halogenated furanosesquiterpenes were present as minor constituents.