Abstract
<title>Abstract</title> <p> Anticancer refers to compounds or agents that are used in the treatment of cancer, exhibiting properties that inhibit the growth of cancer cells. Furthermore, to the pathways connected to cancer, PIM kinases are necessary for several vital biological processes, such as cell differentiation, proliferation, and programmed apoptosis. however, currently available inhibitors suffer from limitations such as adverse effects and limited efficacy. Hence, alternative development of new anticancer agent with better pharmacological properties. In this research, a rational, thinkable series of ten novel chalcone derivatives (H1-H10) was designed and confirmed by using a combined <italic>in silico</italic> approach. ChemDraw2D 8.0 and Chem3D ultra 8.0 were used to design and optimize the ligands, and proprietary molecular docking programs of ArgusLab 4.0.1 were then used to dock the designed molecules with the human Proviral Integration Site (PIM1) complexed with nuvisertib (PDB ID: 4JX3). Moreover, drug-likeness, pharmacokinetic, and toxicity properties have been predicted with Swiss ADME and ProTox-II. The docking scores of the remaining derivatives ranged from − 11.71 to 10.50 kcal/mol, indicating a moderate to strong binding affinity for PIM Kinase. Compound H2 obtained the greatest docking score of -12.83 kcal/mol among those molecules respectively, compared to nuvisertib (-10.9026 kcal/mol). Such compounds showed good interactions. The physicochemical properties, gastrointestinal absorption, blood – brain barrier penetration, and CNS permeability were adequate with favorable results seen during ADMET evaluation, and the toxicity was predicted to be low. In conclusion, the results indicated that chalcone derivatives, notably H1, H2, and H10, appear to be good starting points for creating novel anti-Cancer drugs acting PIM Kinase as inhibitors of and should be thoroughly examined in experimental validation </p>