Phosphoinositide 3-kinase (PI3K) is an attractive target to potentially treat a range of disease states as illustrated by more than 15 inhibitors now in clinical trials. We disclose herein the discovery of a new class of fluoroquinolone derivatives having improved potency toward PI3K.The activity of the compound A3 as an inhibitor of PI3K was further investigated in human tumors cells. Notably, the compound A3 with potent inhibitory activity was low toxic. By compoutational docking studies, it was predicted that, like CAL-101, a known small-inhibitor of PI3K, compound A3 was tightly embedded into the ATP binding pocket with H bonds and π-cation interactions.