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 LD50 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.
Background: COVID-19, a global pandemic caused by SARS-CoV-2 infection, has led researchers around the world to search for therapeutic agents for treatment of the disease. The main protease (M Pro ) of SARS-CoV-2 is one of the potential targets in the development of new drug compounds for the disease. Some known drugs such as chloroquine and remdesivir have been repurposed for treatment of COVID-19, although the the mechanism of action of these compounds is still unknown. In addition to these known drugs, new drug compounds such as 5-O-benzoylpinostrobin derivatives are also potentially used as SARS-CoV-2 M Pro inhibitors. This study aims to determine the potential of 5-O-benzoylpinostrobin derivatives as SARS-CoV-2 M Pro inhibitors, compared with several other compounds used in COVID-19 therapy. Methods: In silico study was carried out by molecular docking of 5-O-benzoylpinostrobin derivatives using Autodock Vina on two SARS-CoV-2 M Pro receptors with PDB IDs of 5R84 and 6LU7. The free energy of binding was calculated and the the interactions of each ligand were analyzed and compared with reference ligand. Results: Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystalized ligands. These three compounds even exhibited promising results in comparison with other reference ligands such as remdesivir and indinavir.
Conclusion:The results of this investigation anticipate that some 5-O-benzoylpinostrobin derivatives have the potential as SARS-CoV-2 M Pro inhibitors.
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