Synthesis, molecular docking, pharmacological evaluation, MD simulation, and DFT calculations of quinazolin-12-one derivatives as PDK1 inhibitors

Abstract

, displayed the strongest binding affinity. The MD simulation showed that Ala162 stands out with a notably high interaction fraction, suggesting that it may be a critical residue for the binding affinity of compound 3f. The analysis of ADMET properties indicated that all inhibitor compounds exhibit favorable pharmacological characteristics, including adherence to Lipinski's Rule of Five (Ro5) as well as the Ghose, Veber, and Egan rules. Additionally, the physicochemical properties demonstrate that all synthesized compounds are capable of human intestinal absorption and have the ability to penetrate the blood-brain barrier (BBB).

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