Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against Haemonchus contortus

Abstract

There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus — a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 ± 0.74 µM) and L4 motility (IC50 = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC50 ≥ 100 µM). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.

Marine Organisms for the Sustainable Management of Plant Parasitic Nematodes

“…(CMB-03107) [ 86 ]. Finally, a moderate to limited inhibition of H. contortus motility was recently documented for fromiamycalin, a pentacyclic guanidine alkaloid, and halaminol A, an acetamide that were isolated from the extracts of the demosponges Monanchora unguilata and Haliclona sp., respectively [ 87 ].…”

Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

“…Although there has been a major focus on synthetic compounds as anthelmintics [8,14], recent studies have shown that natural compounds from both terrestrial and marine environments have shown considerable promise [15][16][17][18][19] due to the diverse biologically active chemotypes in nature [20]. Current estimates indicate that there are >400,000 land plant species and ≥44,000 species of algae [21,22].…”

Actividad antihelmíntica in vivo de terpenos y aceites esenciales en pequeños rumiantes

“…Alcaloides: Con los cuales se dio el inicio formal al estudio de los MSP cuando el farmacéutico alemán Friedrich Sertürner aisló la morfina en el año 1806 (32). Esta familia de MSP posee unas 20,000 estructuras identificadas (39) y sus propiedades AH son materia actual de estudio (40,41).…”