Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives

Abstract

Piperine (1) was obtained from the seeds of Piper nigrum L. It could act as a pan-histone deacetylase (HDAC) inhibitor. This lead compound was structurally modified to six derivatives that exhibited improved HDAC inhibitory activity. Based on the preliminary results, amide derivatives (1e and 1f) with the highest HDAC inhibitory activity were further studied. The results indicated that the derivatives 1e and 1f showed HDAC inhibitory activity with IC50 of 85.61 ± 3.32 µM and 111.27 ± 2.13 µM, respectively. A molecular docking study suggested that piperine (1) had a high selectivity for HDAC1, while 1e and 1f showed high selectivity for HDAC2. These derivatives were predicted to interact with HDAC active site using hydrogen bond, hydrophobic interaction, as well as chelation with Zn2+ . The antiproliferative activity obtained from MTT assay against the HeLa cell line indicated that 1f potentially inhibits HeLa cells with an IC50 of 10.38 ± 2.13 g/mL. These results suggest potential HDAC inhibitors for further development to anti-cancer agents.

Keywords

• piper nigrum l.
• piperine
• piperine derivative
• hdac
• hela cell