Studying Histone Deacetylase Inhibition and Apoptosis Induction of Psammaplin A Monomers with Modified Thiol Group.

Psammaplin A (PsA) is a bromotyrosine disulfide dimer with histone deacetylase (HDAC) inhibition and acts through reduced monomer PsA-SH. We studied the connection of HDAC inhibition, cell growth inhibition, and apoptosis induction of PsA-SH by modifying the -SH group with deletion () or replacement with hydroxamic acid () or benzamide (). PsA-SH inhibits HDAC1/2/3 and loses the HDAC inhibition ability. inhibits HDAC1/2/3/6 while shows selective inhibition of HDAC3. PsA-SH and , but neither nor , induce apoptosis in human leukemia HL-60 cells associated with increased acetylation of Histone H3. PsA-SH and inhibit growth of several solid tumor cell lines in vitro and Lewis lung cancer cell growth in vivo. PsA-SH is a simple scaffold for developing selective HDAC inhibitors and induces apoptosis through inhibiting HDAC1/2.