Molecular Networking-Driven Discovery of Carapins A-H, Bioactive Limonoids from Carapa macrantha Harms (Meliaceae)

Molecular networking-driven investigation of the root, stem bark, and fruit extracts of the medicinal plant Carapa macrantha led to the targeted isolation of seven previously undescribed limonoids (1-7), one new pregnane-type steroid (8), and 17 known compounds (9-25). Structural elucidation was achieved using spectroscopic methods, single-crystal X-ray analyses, and comparison with literature data. Extracts and isolated compounds were assessed in vitro for antiplasmodial activity against the chloroquine-sensitive 3D7 and the multidrug-resistant Dd2 strains of Plasmodium falciparum (Pf3D7 and PfDd2). The dichloromethane (CH₂Cl₂)/methanol (MeOH) (1:1) root extract showed significant activity against PfDd2, with an IC₅₀ value of 10 ± 2 μg/mL and good selectivity over Vero cells (SI > 10). Compounds, 6, 7, 9, 10, and 17 exhibited the best activity, with IC₅₀ values ranging from 5.7 to 22.9 μM against both strains. Compound 17 was the most active one on both strains, with IC₅₀ values of 5.7 ± 0.4 and 9.4 ± 0.4 μM against Pf3D7 and PfDd2 with SI > 7, respectively. These findings highlight C. macrantha as a potential source of antiplasmodial agents.