Plasmodium falciparum is one of the parasites responsible for malaria, a serious and potentially deadly disease. Mitragyna inermis, a plant used to treat malaria in Africa, shows antiplasmodial activity against P. falciparum. Its extracts may target Lactate Dehydrogenase and Protein Kinase G, two enzymes crucial for the parasite’s survival, but the impact of certain pure molecules such as quinovic acid glycosides on these enzymes remains to be determined. To isolate, characterize and evaluate M. inermis compounds for their potential to inhibit Plasmodium LDH and cGMP-dependent protein kinase enzymes through experimental and computational approaches. Phytochemical investigation was conducted using chromatographic techniques, and compounds structures were elucidated by ESI-MS and comprehensive 1&2D NMR analyses. Antiplasmodial activity was assessed on Dd2/3D7 mutant strains. In silico analyses included molecular docking, ADMET prediction, and 100-ns molecular dynamics simulations against LDH and cGMP-dependent protein kinase. Five compounds were isolated and structurally characterized from the stem bark of M. inermis: quinovic acid 3-O-β-D-fucopyranoside (1), quinovic acid 3-O-β-D-glucopyranoside (2), quinovic acid 3-O-β-D-fucopyranosyl-(28→1)-β-D-glucopyranosyl ester (3), olean-12-ene-3β,19β,24-triol (4), and lupeol-3-O-undecanoate (5). Compounds 4 and 5 are reported for the first time from the genus Mitragyna. Compound 3 demonstrated the highest antiplasmodial activity against both PfDd2 and Pf3D7 strains, and exhibited the strongest binding affinity toward PfLDH (−8.2 kcal/mol). MD simulations further confirmed the stability of the C3_PfLDH complex throughout the 100 ns simulation period. These results provide phytochemical and pharmacological support for the ethnomedical use of M. Inermis stem bark for malaria treatment and expand the chemotaxonomic knowledge of the genus Mitragyna.

Background: Plasmodium falciparum, the most virulent malaria parasite, continues to develop resistance to available drugs. Mitragyna inermis (Rubiaceae) is traditionally used in Africa for the treatment of malaria and has shown antiplasmodial activity against P. falciparum. Previous studies on this plant and related species (M. speciosa, M. ciliata) have focused on crude extracts and indole alkaloids, reporting moderate antiplasmodial activity, but the specific contribution of pure quinovic acid glycosides, the major triterpenes glycosides of M. inermis stem bark, to antiplasmodial activity and to inhibition of key parasite enzymes such as lactate dehydrogenase (PfLDH) and protein kinase G (PfPKG) has never been evaluated. Objective: The present study aimed to isolate and characterize compounds from the stem bark of M. inermis and to evaluate their antiplasmodial activity against Pf3D7 and PfDd2 strains and their binding potential to PfLDH and PfPKG through experimental and computational approaches. Methods: Phytochemical investigation was conducted using column chromatography, and structures were elucidated by ESI-MS and 1/2D NMR spectroscopy. Antiplasmodial activity was assessed against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfDd2) strains of P. falciparum. Molecular docking, ADMET prediction, and 100-ns molecular dynamics simulations targeting PfLDH and PfPKG were performed. Results: Five compounds were isolated and identified as quinovic acid 3-O-β-D-fucopyranoside (1), quinovic acid 3-O-β-D-glucopyranoside (2), quinovic acid 3β-O-β-D-fucopyranosyl-28-O-β-D-glucopyranosyl ester (3), olean-12-ene-3β,19β,24-triol (4), and lupeol-3-O-undecanoate (5). Compounds 4 and 5 are reported for the first time from the genus Mitragyna. Compound 3 exhibited the highest antiplasmodial activity against both PfDd2 (35.86 ± 0.83 μM) and Pf3D7 (29.89 ± 3.91 μM) strains, and showed the strongest binding affinity toward PfLDH (−8.2 kcal/mol). MD simulations confirmed the stability of the C3_PfLDH complex throughout the 100 ns simulation period. Conclusions: Compounds 1–4 displayed moderate in vitro antiplasmodial activity against Pf3D7 and PfDd2, with compound 3 being the most active among the isolated constituents. Docking and molecular-dynamics analyses suggested stable interactions of selected compounds with PfLDH and the PfPKG N-terminal cGMP-binding domain. However, these computational findings do not establish direct enzyme inhibition. The results support further investigation of M. inermis triterpenoids as phytochemical scaffolds, including cytotoxicity/selectivity testing, direct target-based assays and structural optimization.

Bryophillin C (BRYOC), a bufadienolide present in plants of the Kalanchoe genus, has been scarcely explored in scientific literature, and its interaction with proteins involved in breast cancer (BCa) pathophysiology is yet to be understood. This study aimed to explore BRYOC’s anticancer potential in BCa using computational methods. Density functional theory (DFT) analysis revealed a HOMO–LUMO gap of 4.59 eV, suggesting moderate chemical reactivity and polarizability. The predicted ADMET profile suggested good oral bioavailability and limited distribution potential in the body. Databases helped identify BRYOC targets and genes linked to BCa, which are mainly involved in protein autophosphorylation and transmembrane receptor protein tyrosine kinase activity. A protein–protein interaction network was constructed to identify the main targets connecting BRYOC and BCa. Molecular docking studies indicated that SRC, PIK3CA, and ESR1 exhibited the most favorable binding affinities. To assess complex stability, a 100 ns molecular dynamics simulation was conducted, followed by a detailed examination of key structural parameters, such as the root-mean-square deviation and radius of gyration. MM/GBSA calculations predicted favorable binding free energies for SRC and ESR1 ligands. These results emphasize the importance of these proteins as therapeutic targets in the pathophysiology of BCa and serve as a precedent for future studies focused on BRYOC and its possible anticancer effects.

Psoralen (PSN), a naturally occurring furocoumarin, was evaluated for its antiemetic potential using integrated in vivo and in silico approaches, considering the limitations of currently available antiemetic agents. The antiemetic activity of PSN was investigated in a copper sulfate–induced emesis model using 2‐day‐old chicks ( Gallus gallus domesticus ). A dose‐dependent experimental design was employed with PSN (5, 10, and 20 mg/kg), alongside standard antiemetics (domperidone 6 mg/kg, ondansetron (OND) 5 mg/kg, and hyoscine 21 mg/kg) and combination treatments. Latency to first retch and total retching episodes were recorded, and percentage inhibition was calculated. Molecular docking was performed against D ₂ , D ₃ , 5‐HT _3A , and muscarinic (M ₁ –M ₅ ) receptors. ADMET and toxicity profiles were predicted using SwissADME and ProTox‐3.0. PSN produced a significant, dose‐dependent reduction in retching. The 20 mg/kg dose showed 65.60% inhibition of retches compared to control. Combination treatment with OND further enhanced inhibition (65.60%). Docking analysis revealed that PSN exhibited the strongest binding affinity toward the D ₂ receptor (−8.8 kcal/mol), followed by M ₅ (−8.1 kcal/mol) and 5‐HT _3A (−7.7 kcal/mol). Pharmacokinetic prediction indicated high gastrointestinal absorption and favorable drug‐likeness properties. PSN demonstrates significant antiemetic activity in a validated chick emesis model, supported by moderate binding affinity toward key emesis‐related receptors. While docking findings suggest possible receptor interactions, further mechanistic and translational studies are required to confirm the molecular basis of its activity.