Chemical biology & drug design

Design, synthesis, biological evaluation, and molecular docking of novel benzopyran and phenylpyrazole derivatives as Akt inhibitors.

PMID 25453512


By inspiration of good Akt1 inhibitory and cytotoxic activity of our previously screened hits 1 and 2, a series of novel benzopyrans 3a-c, 4 and phenylpyrazoles 5a-c, 6a-b, and 7 were designed, synthesized, and biologically evaluated for their in vitro Akt1 inhibitory and cytotoxic activity. The results revealed that all of these compounds showed moderate-to-excellent antiproliferative effects against the tested cancer cell lines (i.e. HL-60, OVCAR, PC-3, and HepG2). Among them, compounds 3a and 3c exhibited preferable Akt1 inhibitory activities (IC(50) of 3a and 3c are 6.18 and 5.28 μm, respectively), while compounds 4, 5a-c, 6a-b, and 7 only showed weak Akt1 inhibitory activities. Consequently, we used molecular docking and dynamic simulation to propose a mode of binding between Akt1 and the 3c compound.