Sarcocephalobixin, a novel DPPH radical scavenger and antiplasmodial apocarotenoid from Nauclea latifolia Sm.: in vitro studies, molecular docking, molecular dynamics and drug-likeness prediction

The present study aimed to isolate chemical constituents from the root wood and stem bark of Nauclea latifolia Sm., and to evaluate their antiplasmodial and antioxidant activities. The antiplasmodial activity was assessed against chloroquine-sensitive ( Pf 3D7) and multi-resistant ( Pf Dd2) strains of Plasmodium falciparum , while antioxidant potential was evaluated using the DPPH radical scavenging assay. Phytochemical investigation of the stem bark led to the isolation of a new apocarotenoid, (2 E ,4 E ,6 E ,8 E ,10 E ,12 E ,14 E ,17 E ,19 E )-21-methoxy-4,8,13,18-tetramethyl-21-oxohenicosa-2,4,6,8,10,12,14,17,19-nonaenoic acid ( 1 ), trivially named sarcocephalobixin, along with one triterpenoid ( 2 ), two indole alkaloids ( 3 – 4 ), and one saponin ( 5 ). In addition, two saponins ( 6 – 7 ) were isolated from the root wood. The structures were elucidated based on MS and NMR spectroscopic analyses. All seven compounds exhibited notable antiplasmodial activity (IC 50 < 50 µg/mL) against both parasite strains while artemisinin remains substantially more potent. Strictosamide ( 3 ) showed the highest activity, with IC 50 values of 3.0 ± 0.3 µg/mL ( Pf 3D7) and 4.3 ± 0.4 µg/mL ( Pf Dd2). In the DPPH assay, compound 1 displayed strong antioxidant activity with 88.7% inhibition, compared to ascorbic acid (95.5%). Molecular docking studies revealed that strictosamide ( 3 ) interacts strongly with P. falciparum cysteine protease falcipain-2 (3bpf) and dihydroorotate dehydrogenase ( Pf DHODH, 7kz4), with binding energies of −7.1 and −7.6 kcal/mol, respectively. Molecular dynamics (MD) simulations of the 3–3BPF complex confirmed a stable induced-fit binding mode, supported by a binding free energy of −28.9 ± 3.4 kcal/mol. Selectivity analysis suggested that compound 1 may preferentially target FP-2, while compounds 1 – 3 showed selectivity toward Pf DHODH over the human homolog. Overall, the isolated compounds from N. latifolia demonstrate promising antiplasmodial and antioxidant properties, supporting their potential as lead scaffolds for antimalarial drug development. ADMET analysis further supported their drug-like characteristics.