Computational analysis of benzofuran-2-carboxlic acids as potent Pim-1 kinase inhibitors

Context: The three Pim serine/threonine kinases (Pim-1, Pim-2, and Pim-3) belong to a small family of kinases that regulate numerous signaling pathways fundamental to the development of tumors. Pim kinases' overexpression has been reported in numerous solid and hematological tumors and, in particular, prostate cancer (Pim-1). Objectives: This study investigated the binding modes of benzofuran-2-carboxlic acids against Pim-1 kinase, hence providing useful information for the active inhibition of it. Materials and methods: In present study, molecular docking approach via MOE-Dock program was applied to predict the binding interactions of some known Pim-1 kinase inhibitors. First validation of the docking protocol was carried out by calculating RMSD for the co-crystallized and docked ligands. Using the same protocol, all the compounds were docked into the active site of Pim-1 kinase. Results: All the compounds showed significant interactions and good correlation with the experimental data. The results illustrate that compounds with optimum basicity and relevant distance between the acidic and basic groups showed optimum interactions with the active site residues of Pim-1 kinase. Conclusion: We hope that this study will be helpful in designing new, structurally diverse and more potent compounds for the active treatment of prostate cancer and other related diseases caused by deregulation of Pim-1 kinase.