Phytochemical Investigation of Celtis Mildbraedii Engl and Exploratory In Vitro and In Silico Evaluation against Schistosoma Mansoni

Abstract Schistosomiasis remains a major neglected tropical disease, underscoring the need to expand the chemical space available for antischistosomal drug discovery. Using modern methods in phytochemistry, a chemical investigation of the stem bark and roots of Celtis mildbraedii Engl. (Cannabaceae) led to the isolation and structural characterization of 17 secondary metabolites, including a previously unreported dicarboxylic acid (1) named celtic acid, a previously unreported paraconic acid (2) named milbraedic acid, a monounsaturated fatty acid (3) (9R,10E,12R,13S)-9,12,13-trihydroxy-10-octadecanoic acid, reported for the first time from natural sources, and its previously unreported hydrogen-bonded dimer (4), named Niemeyong acid dimer, together with 13 known compounds (5–17), belonging to several classes of secondary metabolites, including triterpenoids, xanthones, phenolic amides, phenolic acids, alkaloids and fatty acid derivatives. The isolated metabolites were subjected to exploratory in vitro phenotypic screening against adult worms and newly transformed schistosomula of Schistosoma mansoni. Three compounds, including corosolic acid (11), compound 3, and gallic acid (14), exhibited measurable activity against adult worms, with EC50 values of 158.6, 302.6, and 764.21 μM, respectively. No activity was observed against larval stages. The active metabolites did not display cytotoxicity in mammalian cell lines or lethality in Caenorhabditis elegans at the highest tested concentrations (2000 μM). In silico analyses indicated generally acceptable drug-likeness profiles, predicted gastrointestinal absorption, and low acute oral toxicity in rats. Although the antiparasitic potency was modest, the combined chemical and biological evaluation expanded the repertoire of natural products assessed against S. mansoni and provides a foundation for future structure-based optimization.