In an endeavor to identify small molecules for the management
of
non-small-cell lung carcinoma, 10 new hydrazone derivatives (3a–j) were synthesized. MTT test was conducted to examine
their cytotoxic activities against human lung adenocarcinoma (A549)
and mouse embryonic fibroblast (L929) cells. Compounds3a,3e,3g, and3iwere determined
as selective antitumor agents on A549 cell line. Further studies were
conducted to figure out their mode of action. Compounds3aand3gmarkedly induced apoptosis in A549 cells. However,
both compounds did not show any significant inhibitory effect on Akt.
On the other hand,in vitroexperiments suggest that
compounds3eand3iare potential anti-NSCLC
agents acting through Akt inhibition. Furthermore, molecular docking
studies revealed a unique binding mode for compound3i(the strongest Akt inhibitor in this series), which interacts with
both hinge region and acidic pocket of Akt2. However, it is understood
that compounds3aand3gexert their cytotoxic
and apoptotic effects on A549 cellsviadifferent
pathway(s).