Design, synthesis and anticancer activity of piperazine hydroxamates and their histone deacetylase (HDAC) inhibitory activity

Six compounds were synthesized with piperazine in linker region and hydroxamate as Zinc Binding Group (ZBG). They were screened against three cancer cell-lines (NCIH460; HCT116; U251). Compounds 5c and 5f with GI50 value of 9.33 ± 1.3 μM and 12.03 ± 4 μM, respectively, were tested for their inhibitory potential on hHDAC8. Compound 5c had IC50 of 33.67 μM. Compounds were also screened for their anticancer activity against HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitors in them. Compound 5c had IC50 of 0.6 μM at 48 h.

Compound 5c has shown mean GI50: 9.33 ± 1.3 μM against NCIH460, HCT116 and U251 cell lines and IC50: 33.67 μM against HDAC8. It also inhibited HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitor.Figure optionsDownload as PowerPoint slide