Naturally Occurring 8ß,13ß-kaur-15-en-17-al and Anti-Malarial Activity from Podocarpus polystachyus Leaves.

Despite much interest and studies toward the genus Podocarpus , the anti-malarial evaluation of Podocarpus polystachyus 's phytoconstituents remains lacking. Herein, the phytoconstituents of P. polystachyus leaves and their anti-malarial effect against Plasmodium falciparum were investigated for the first time. One new natural product, 8ß,13ß-kaur-15-en-17-al ( 1 ), along with three known compounds, 8ß,13ß-kaur-15-en-17-ol ( 2 ) and 13ß-kaur-16-ene ( 3 ), and α-tocopherol hydroquinone ( 4 ) were isolated via HR-ESI-MS and NMR analyses. Compounds 1 and 2 inhibited P. falciparum growth at 12 and 52 µM of IC 50 , respectively. Their anti-malarial activity was associated with the in silico P. falciparum lactate dehydrogenase ( Pf LDH) inhibition. Molecular docking of ligands 1 and 2 with the putative target Pf LDH revealed ~-2 kcal/mol of binding energies more negative than the control. Molecular dynamic simulations (100 ns) showed equal or smaller deviation values (RMSD, RMSF, Rg) and stronger interactions of Pf LDH- 1 and Pf LDH- 2 complexes via at least one consistent H-bond than the control. Additionally, a slightly increased Pf LDH H-bond profile in their interactions improved the Pf LDH dynamic and structural stabilities. Overall, this study supports the relevance of 1 and 2 as plasmodial growth inhibitors with their putative anti- Pf LDH activity, which could be a potential scaffold for developing anti-malarial drugs.