QSAR Modeling and Molecular Docking Studies of 3,5-Disubstituted Indole Derivatives as Pim1 Inhibitors for Combating Hematological Cancer

Cancer has become a global health concern, with escalating mortality rates in the 21st century, leading the World Health Organization to recognize it as one of the deadliest diseases. In their search for new anticancer therapeutic agents, researchers have identified the 3,5-disubstituted Indole derivatives as potential therapeutic agents capable of targeting the Proviral integration of moloney (Pim) kinases that correlate to hematological cancers. This study aims to investigate a series of 3,5-disubstituted indole derivatives as potent inhibitors of Pim1 kinase. Different computational chemistry techniques were utilized, including 2D-QSAR and molecular docking, to design novel inhibitors for targeting Pim1. The analysis of 2D-QSAR results showed that the inhibitory activity might be predicted with high accuracy (R²test = 0.96) using a classical statistical modeling technique, namely partial least squares regression.The six inhibitors that were identified as highly bio-active, were subjected to the docking study, and the results highlighted the important Pi-Alkyl interactions rising between the ligands and the Pim-1 kinase receptor (PDBcode:5DWR),which may enhance the binding of the ligand to a hydrophobic pocket on the target receptor. Overall, the combination of 2D-QSAR, moleculardocking, and ADMETanalysis has provided valuable insights and potential avenues for further exploration in the development of effective hematologicalanticancer agents.