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
Luiz R. G. Filho, Gustavo Y. Miyake and Carlos H. T. P. da Silva
Affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, Monte Alegre, 14040-903, Ribeirão Preto, Brasil.
Keywords: PIM-1 inhibitors, density functional theory, ADMET, structure-based drug design, docking, pharmacophore
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.
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