Density Functional Theory, Docking, Bioisosteric Replacement, Pharmacophore Perception, Physical Chemical Analyses of the Interactions of Novel PIM-1 Inhibitors with Suitable Pharmacokinetic Properties for Cancer Treatment

摘要

We have investigated novel PIM-1 hybrid inhibitors in cancer using drug design and ADMET studies. Different modeling methods and medicinal chemistry strategies were used including isosteric replacement. We have worked with active inhibitors reported in the literature investigating pharmacophore models, physicochemical and pharmacokinetic properties. We have applied Lipinski's rule of five and synthetic accessibility. Flexible docking simulations were done using GOLD in order to predict the binding modes of the novel hybrids inside the PIM-1 active site. Our results suggest two candidates as promising novel PIM-1 inhibitors with good pharmacotherapeutic profiles for the fight against cancer.