The indoles plant growth hormones have exhibited potentially antitumor activities. However, the targets of these indoles have not been clearly elucidated. By introduction of hydroxamic acid group to the structure of indolebutyric acid, the derived molecule (IBHA) exhibited potent HDAC2 (IC50 value of 0.32 ± 0.02 µM) and HDAC3 (IC50 value of 0.14 ± 0.01 µM) inhibitory activities compared with SAHA (IC50 value of 1.25 ± 0.06 µM and 0.97 ± 0.04 µM against HDAC2 and HDAC3). In the antiproliferative assays, the tested hematologic cell lines (U937 and K562) are more sensitive to IBHA than the solid tumor cell lines (MDA-MB-231 and PC-3). In the docking studies, the derived molecule (IBHA) could bind to the active site of human HDAC2 and HDAC3 by strong H-bond interactions and hydrophobic interactions. Pharmacophore mapping results revealed that properties of IBHA matches the receptor (HDAC3) based pharmacophore model.