Phytotoxic, antifungal and antiplasmodial properties of diterpenes isolated from Copaifera resins

Authors: RIBEIRO, VICTOR - Orise Fellow; Meepagala, Kumudini; Tamang, Prabin; BASTOS, JAIRO - Universidad De Sao Paulo; Bajsa Hirschel, Joanna

Submitted to: Journal of Natural Pesticide Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/2025
Publication Date: 9/22/2025
Citation: Ribeiro, V., Meepagala, K.M., Tamang, P., Bastos, J., Bajsa Hirschel, J.N. 2025. Phytotoxic, antifungal and antiplasmodial properties of diterpenes isolated from Copaifera resins. Journal of Natural Pesticide Research. 14:100161. https://doi.org/10.1016/j.napere.2025.100161.
DOI: https://doi.org/10.1016/j.napere.2025.100161

Interpretive Summary: This study presents the potential of natural compounds called diterpenes, found in copaiba oil-resins, for use in agriculture and medicine. Four diterpenes were tested and showed promising results: some were effective in stopping weed growth, while others inhibited a fungus that affects strawberries. Additionally, computer-based simulations suggested that two of these compounds could interfere with a key enzyme in the malaria parasite, indicating possible antimalarial activity. Importantly, these compounds also met criteria that suggest they could be developed into safe and effective drugs. Among them, one compound stood out as a strong candidate for both herbicide and antimalarial development.

Technical Abstract: Diterpenes are bioactive secondary metabolites with diverse pharmacological and agricultural applications. In this study, four diterpenes—ent-polyalthic acid (1), ent-dihydroagathic acid (2), ent-kaurenoic acid (3), and ent-kaurenol (4)—were isolated from copaiba oil-resins and evaluated for their phytotoxic, antifungal, and antiplasmodial activities. Phytotoxicity assays revealed herbicidal activity against Agrostis stolonifera, with ent-polyalthic acid and ent-kaurenoic acid exhibiting the highest efficacy, inhibiting seed germination. ent-dihydroagathic acid also showed phytotoxicity against Lemna paucicostata with IC50 value of 3.8 µM. All compounds inhibited the growth of Colletotrichum fragariae in a bioautography bioassay, with ent-kaurenoic acid exhibiting the highest activity. Molecular docking studies demonstrated favorable binding affinities of ent-polyalthic acid and ent-dihydroagathic acid to Plasmodium falciparum lactate dehydrogenase, suggesting competitive inhibition with NADH. Pharmacokinetic assessments indicated adherence to Lipinski’s Rule of Five and suitable properties for oral bioavailability. These findings undescore the potential of these diterpenes, particularly ent-polyalthic acid, as lead compound for herbicidal and antimalarial drug development.