Phytocompound inhibitors of caspase 3 as beta-cell apoptosis treatment development option: An In-silico approach

The prevalence of Diabetes mellitus (DM) is continuously rising worldwide. Among its types, type I is characterized by the destruction of beta cells triggered by various mechanisms, including the activation of Caspase 3. Studies have demonstrated the crucial role of Caspase 3 in initiating the apoptosis of beta cells in DM. Our research aims to identify possible phytocompounds inhibitors of Caspase 3 using computational approach. We obtained 3D structures of Caspase 3 and 6511 phytocompounds from the Protein Data Bank and the African Natural Products Database, respectively. The phytocompounds were assessed for druglikeness properties, topological polar surface area, and preliminary toxicity using DataWarrior. The phytocompounds were subjected to molecular docking simulation (MDS) at Caspase 3 active site using AutoDock-Vina. The frontrunner phytocompounds obtained from the MDS were subjected to protease inhibition prediction on Molinspiration. The pharmacokinetics of the phytocompounds were assessed on SwissADME. The in-depth computational toxicity profile of the phytocompounds was evaluated on the pkCSM web. The binding interactions of the phytocompounds with Caspase 3 were assessed with Discovery Studio Visualizer and Maestro. Seventeen phytocompounds were found to have no violation of Lipinski's rule and had no toxicity based on the preliminary assessment, have better binding affinity and protease inhibitory prediction scores than the references, have optimistic bioactivity radar prediction and similar amino acids interaction, in comparison with the references. Further studies, which include in-vitro and in-vivo studies, will be carried out to validate the results of this study.