Background: Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5- O -benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5- O -benzoylpinostrobin derivative. Methods: Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters. Results: In general, absorption parameters indicate that the 5- O -benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5- O -benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD ₅₀ value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1. Conclusions: Overall, the 5- O -benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5- O -benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

Observation of molecular docking results was generally performed by analyzing the docking score and the interacting amino acid residues separately either in tables or graphs. Sometimes it was not easy to rank the tested ligands’ docking results, especially if there were many ligands. This study aims to introduce a new way to analyze docking results with a two‐dimensional graph between the difference in docking score and the similarity of ligand‐receptor interactions. Molecular docking was performed with one reference ligand and several test ligands. The docking score difference was obtained between the test and the reference ligands as the graph’s x‐axis. Meanwhile, the y‐axis contains the similarity of ligand‐receptor interactions, obtained from the ratio of amino acid residues and the types of interactions between the test and reference ligands. Docking result analysis was more straightforward because two critical parameters were presented in one graph. This graph could be used to support the analysis of the docking results.

Objectives: This study was designed to verify the antiangiogenic activity of ferulic acid (FA) and its potency to inhibit cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expression in the chorioallantoic membrane (CAM) model. Moreover, we verified its mechanism of action by docking the molecule on COX-2, tyrosine kinase, and VEGF-2 proteins in silico. Materials and Methods: An antiangiogenesis assay of FA at doses of 30, 60, and 90 mu g was performed using the CAM of chicken eggs that were 9 days old and stimulated by 60 ng of basic fibroblast growth factor. Celecoxib (60 mu g) was used as the reference drug. The inhibitory activity on VEGF and COX-2 expression was determined by immunohistochemistry assay. Molecular docking of FA was accomplished by Molegro Virtual Docker program ver. 5.5 on COX-2 enzyme (PDB ID 1CX2), tyrosine kinase receptor (PDB ID 1XKK), and VEGF-2 receptor (PDB ID 4ASD). Results: FA at doses of 30, 60, and 90 mu g significantly prevented angiogenesis in the CAM model, which was represented as inhibitory activity against endothelial cells of blood vessels (42.6-70.7%) and neovascularization (43.0-86.6%). The inhibitory activity of FA against VEGF expression was stronger than its action on COX-2 expression. Molecular docking on VEGF-2 receptor resulted in an RS value of FA of-73.844 kcal/mol and for celecoxib it was-94.557 kcal/mol. The RS value on tyrosine kinase of FA was-84.954 kcal/mol, while on celecoxib it was-93.163 kcal/mol. Docking on COX-2 receptor gave an RS value of FA of-73.416 kcal/mol, while for celecoxib it was-118.107 kcal/mol. Conclusion: Reductions in VEGF-2 and COX-2 expression due to treatment with FA at the dose range 30-90 mu g appeared to be related to angiogenesis inhibition, which was shown by two parameters, namely inhibition of neovascularization and endothelial cell growth in blood vessels. It was concluded that FA is a promising antiangiogenic therapeutic agent especially at the early stage, and this activity can arise from inhibitory action on COX-2 and VEGF-2

Background: Boesenbergia pandurata or fingerroot is known to have various pharmacological activities, including anticancer properties. Extracts from these plants are known to inhibit the growth of cancer cells, including breast cancer. Anti-breast cancer activity is significantly influenced by the inhibition of two receptors: ER-α and HER2. However, it is unknown which metabolites of B. pandurata play the most crucial role in exerting anticancer activity. Objective: This study aimed to determine the metabolites of B. pandurata with the best potential as ER-α and HER2 inhibitors. Method: The method used was molecular docking of several B. pandurata metabolites to ER-α and HER2 receptors, followed by an ADMET study of several metabolites with the best docking results. Results: The docking results showed eight metabolites with the best docking results for the two receptors based on the docking score and ligand-receptor interactions. Of these eight compounds, compounds 11 ((2S)-7,8-dihydro-5-hydroxy-2-methyl-2-(4''-methyl-3''-pentenyl)-8-phenyl-2H,6H-benzo(1,2-b-5,4- b')dipyran-6-one) and 34 (geranyl-2,4-dihydroxy-6-phenethylbenzoate) showed the potential to inhibit both receptors. Both ADMET profiles also showed mixed results; however, there is a possibility of further development. Conclusion: In conclusion, the metabolites of B. pandurata, especially compounds 11 and 34, can be developed as anti-breast cancer agents by inhibiting ER-α and HER2.

Background: Previous studies have shown that 5- O -benzoylpinostrobin derivatives is a potential anti-breast cancer, with the highest potential being the HER2 inhibitors, is a protein’s member of the epidermal growth factor receptor (EGFR) family. Overexpression of EGFR itself is known to be one of the causes of other cancer, including non-small cell lung cancer (NSCLC). Thus, it is possible that 5- O -benzoylpinostrobin derivatives can also inhibit the overexpression of EGFR in NSCLC. In the case of NSCLC, mutations of EGFR are often found in several amino acids, such as L858R, T790M, and V948R. This study aimed to determine the potential of 5-O-benzoylpinostrobin derivatives as an inhibitor of wild type and L858R/T790M/V948R-mutant EGFR. Methods: Docking was performed using AutoDock Vina 1.1.2 on both wild type and L858R/T790M/V948R-mutant EGFR. Parameters observed, consisted of free energy of binding (ΔG) and amino acid interactions of each ligand. Results: Docking results showed that all 5- O -benzoylpinostrobin derivatives showed a lower ΔG for both wild type and L858R/T790M/V948R-mutant EGFR, with the lowest ΔG shown by 4-methyl-5- O -benzoylpinostrobin and 4-trifluoromethyl-5- O -benzoylpinostrobin. Both the ligands have the similarity of interacting amino acids compared to reference ligands between 76.47 and 88.24%. Specifically, the ΔG of all test ligands was lower in mutant EGFR than in the wild type, which indicates the potential of the ligand as EGFR inhibitors where a mutation to EGFR occurs. Conclusions: These results confirm that 5- O -benzoylpinostrobin derivatives have the potential to inhibit EGFR in both wild type and L858R/T790M/V948R-mutant.

Preparation and characterization of a novel cocrystal of atorvastatin calcium with succinic acid coformer were successfully performed. This research aims to modify the crystalline form of atorvastatin calcium through cocrystallization with succinic acid coformer. The cocrystal was prepared by a solvent evaporation method and characterized by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The atorvastatin calcium-succinic acid cocrystal has new crystalline peaks at 2θ of 12.9, 18.2 and 26.7° indicating the formation of a new crystalline phase. The cocrystal showed the melting point at 205.7 °C with an enthalpy of fusion 30.2 J/g which is different from the initial components. The FTIR spectra of cocrystal showed the shifting of absorption peaks of groups of initial components indicating of formation of atorvastatin calcium-succinic acid cocrystal through acid–amide intermolecular hydrogen bond interactions. The solubility and dissolution test showed that the cocrystal has solubility and dissolution rate significantly higher than the solubility and dissolution rate of pure atorvastatin calcium.