The
p110
a, catalytic subunit of PI3K
a, was the primary phosphoinositide 3-kinases (PI3Ks) isoform involved in
oncogenic RTK signaling and tumorigenesis. In this study, the three-dimensional
quantitative structure-activity relationship (3
D-QSAR), molecular docking and molecular dynamics simulation were
employed to study the binding mode between 3-phenylsulfonylaminopyridine derivatives
and PI3K
a. The stable and reliable 3
D-QSAR models were constructed based on the
application of the comparative molecular field analysis (CoMFA) model (
q2 = 0.704,
r2 = 0.994) and comparative
molecular similarity index analysis (CoMSIA) model (
q2 = 0.804,
r2 = 0.996). The contour maps illustrated relationship between structure and
biological activity. The conformation obtained after MD simulation was more
stable than the docked conformation. MD simulation was performed in a more
realistic environment, and was much closer to physiological conditions. As a result, five novel PI3K
a inhibitors were designed
with better biological activity than the template compound
8.