Discovery of new pyridine-quinoline hybrids as competitive and non-competitive PIM-1 kinase inhibitors with apoptosis induction and caspase 3/7 activation capabilities.

New quinoline-pyridine hybrids were designed and synthesised as PIM-1/2 kinase inhibitors. Compounds , , , and showed low cytotoxicity against normal human lung fibroblast Wi-38 cell line and potent anticancer activity against myeloid leukaemia (NFS-60), liver (HepG-2), prostate (PC-3), and colon (Caco-2) cancer cell lines. In addition, and significantly induced apoptosis with percentage more than 66%. Moreover, and significantly induced caspase 3/7 activation in HepG-2 cell line. Furthermore, and showed potent PIM-1 kinase inhibitory activity. While, showed potent PIM-2 kinase inhibitory activity. Kinetic studies using Lineweaver-Burk double-reciprocal plot indicated that , , and behaved as competitive inhibitors while behaved as both competitive and non-competitive inhibitor of PIM-1 kinase enzyme. Molecular docking studies indicated that, affinity came in coherence with the observed inhibitory activities against PIM-1/2 kinases.