ADMET PREDICTION AND MOLECULAR DOCKING SIMULATION OF PHYTOCONSTITUENTS IN Boesenbergia rotunda RHIZOME WITH THE EFFECTOR CASPASES TO UNDERSTAND THEIR PROTECTIVE EFFECTS.

Acute kidney injury is a condition when kidney function decreased abruptly, characterized by e.g. a decrease in the glomerular filtration rate. This condition is due to the activation of various signaling pathways, such as effector caspases, and thus can reverse kidney damage by interacting with these proteins, and eventually inhibiting the apoptotic process. This study aims to determine the molecular interactions of eight phytoconstituents in B. rotunda rhizome with the active binding pocket of caspase-3 and-7 and to predict the ADMET profile of these ligands. Results indicated that all ligands could occupy the binding pocket of both caspases, similar to those of caspase inhibitors, which means that these compounds could inhibit the apoptotic signaling pathway, thus protecting the cell. However, these ligands indicate a better docking score with caspase-7 than with caspase-3. Of all ligands, 4-hydroxypanduratin A and panduratin A showed the best affinity (-8.3 kcal/mol and -8.5 kcal/mol, respectively). ADMET prediction revealed that the excellent oral bioavailability belongs to 4-hydroxypanduratin A and pinostrobin (HIA >99%; Caco2 >70 μm/sec; BBB <1; PPB <50%). [ABSTRACT FROM AUTHOR]