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

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.

ADME profiling, molecular docking, DFT, and MEP analysis reveal cissamaline, cissamanine, and cissamdine from Cissampelos capensis L.f. as potential anti-Alzheimer's agents

“…The obtained root mean square deviations (RMSDs) were within an acceptable range, under 2 Å, as noted in ref. 56–58. Such validation lends credibility to the docking parameters used for predicting the binding orientations of new proaporphine alkaloids (cissamaline, cissamanine, cissamdine) with proteins associated with AD.…”

Identification and Absorption–Distribution–Metabolism–Excretion–Toxicity Prediction of Potential MTHFD2 Enzyme Inhibitors from Urtica dioica Ethanolic Leaf Extract

“…In order to facilitate a molecular docking study, the enzyme target's 3D structures underwent preprocessing procedures. Biovia Discovery Studio Visualizer [46] was used to remove heteroatoms and non-essential water molecules [47][48][49][50][51]. The resulting structure was saved in PDB format.…”

“…The obtained RMSD was within an acceptable range, under 2 Å, as noted in refs. [47][48][49][50][51]54,[80][81][82]. Such validation lends credibility to the docking parameters used for predicting the binding orientations of the identified compounds [47][48][49][50][51]54,[80][81][82].…”

In Vitro and In Silico Analysis of the Anticancer Effects of Eurycomanone and Eurycomalactone from Eurycoma longifolia

“…The resulting score energies were −7.93 kcal/mol and −8.19 kcal/mol, respectively, with small root mean square deviations (RMSDs) of 0.98 Å for TNF-α and 0.62 Å for DHFR (Table 5). An RMSD value of ≤ 2.0 Å is typically considered acceptable in the literature [45][46][47][48][49]. Based on these results, we applied the same docking parameters to dock eurycomanone and eurycomalactone.…”

“…With MODELLER 9.18 [79], all missing residues in the crystal structures have been added and refined. Using the PDB2PQR web service (https://pdb2pqr.poissonboltzmann.org/pdb2 pqr, accessed on 14 October 2022), additional treatments were performed on the crystal structures, including reconstructing missing atoms, assigning atomic charges, and radii using the SWANSON force field (AMBER ff99 charges with optimized radii) [47][48][49]80]. At pH 7.40, PROPKA3 [81], which is the most commonly used empirical pKa predictor, was used to determine the protonation states of the ionisable groups in the crystal structures.…”