Naturally Occurring 8ß,13ß-kaur-15-en-17-al and Anti-Malarial Activity from Podocarpus polystachyus Leaves
Mira Syahfriena Amir Rawa, Mohammad G. Al‐Thiabat, Toshihiko Nogawa, Yushi Futamura, Akiko Okano, Habibah A. Wahab
Abstract
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 IC50, respectively. Their anti-malarial activity was associated with the in silico P. falciparum lactate dehydrogenase (PfLDH) inhibition. Molecular docking of ligands 1 and 2 with the putative target PfLDH 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 PfLDH-1 and PfLDH-2 complexes via at least one consistent H-bond than the control. Additionally, a slightly increased PfLDH H-bond profile in their interactions improved the PfLDH dynamic and structural stabilities. Overall, this study supports the relevance of 1 and 2 as plasmodial growth inhibitors with their putative anti-PfLDH activity, which could be a potential scaffold for developing anti-malarial drugs.