Design, synthesis and antitumor effects of novel benzimidazole derivatives as PI3K inhibitors

Blocking the PI3K/Akt pathway has been widely recognized as an attractive cancer therapeutic strategy because of its crucial role in cell growth and survival. This study presents the synthesis of 24 new 5-Methoxy-6substituted-1H-benzimidazole derivatives (4a-4x) and the evaluation of their anti-proliferative activities against A549, Siha, MCF-7, HepG2, PC3, and HCT-116 tumor cell lines through MTT assay. Compound 4w exhibited superior anti-tumor activity against the A549 cells with IC50 values of 1.55 +/- 0.18 mu M, and better than the BKM120 (IC50 = 9.75 +/- 1.25 mu M). Further studies indicated that 4w could induce G0/G1 phase arrest, cell apoptosis, and down-regulate expression of p-PI3K and p-Akt. These results indicate that 4w could be served as a lead compound of PI3K inhibitor for the treatment of human lung cancers.