Molecular Networking-Driven Discovery of Carapins A–H, Bioactive Limonoids from <i>Carapa macrantha</i> Harms (Meliaceae)

Abstract

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.