Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC–MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.

Background/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR–biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by ¹H and ¹³C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC₅₀/96 h values of 47.2 and 46.1 µM for male and female worms respectively, and totally suppressed egg laying with 60 µM, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control.