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

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