In Silico exploration of 16-demethoxy-20′-epi-serpentinine from Picralima nitida as a potential inhibitor of Plasmodium falciparum enoyl acyl carrier protein reductase
Yemi Adekola Adekunle, Kehinde Foluke Paul-Odeniran, Babatunde B. Samuel, Suji Adetuwo · In Silico Research in Biomedicine · 2025
There is a growing concern regarding the resistance of malaria-causing parasites to current antimalarial drugs. This is prompting global efforts to develop new treatments. This study aims to investigate the inhibitory potential of Picralima nitida compounds against Plasmodium falciparum enoyl acyl carrier protein reductase (P f ENR) and lactate dehydrogenase ( Pf LDH) using computational models. Molecular docking studies were carried out on twenty-three compounds previously identified from P. nitida against the selected proteins. The most promising compound, an alkaloid, was further subjected to molecular dynamics (MD) simulations at 200 nanoseconds. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) binding free energy calculation was carried out. In addition, the compliance of the compound with Lipinski’s Rule of 5 was evaluated. The results of the docking study showed that 16-Demethoxy-20′‑epi-serpentinine (DES) had the best binding affinity of –12.1 and –8.0 kcal/mol for P f ENR and Pf LDH, respectively. Estimation of the MMPBSA-binding free energy showed that DES elicited favourable binding (–49.41±0.39 and –46.35±0.63 kcal/mol for P f ENR and Pf LDH, respectively), relative to chloroquine (–22.56±0.58 and –36.21±0.34 kcal/mol for P f ENR and Pf LDH, respectively). Analysis of MD parameters (C-α RMSD, RMSF, RoG, and SASA) indicated that DES induced structural changes in the proteins. This study identifies and provides theoretical evidence for the alkaloid 16-demethoxy-20′‑epi-serpentinine as a potential inhibitor of P. falciparum enoyl acyl carrier protein reductase and P. falciparum lactate dehydrogenase. This preliminary study on 16-demethoxy-20′‑epi-serpentinine may open up more studies on the compound to experimentally validate its antiplasmodial activities in both cell-based and enzyme-based models.