Largazole and analogues with modified metal-binding motifs targeting histone deacetylases: synthesis and biological evaluation Article (Faculty180)

cited authors

  • Bhansali, Pravin; Hanigan, Christin L; Casero, Robert A; Tillekeratne, L M


  • The histone deacetylase inhibitor largazole 1 was synthesized by a convergent approach that involved several efficient and high yielding single pot multistep protocols. Initial attempts using tert-butyl as thiol protecting group proved problematic, and synthesis was accomplished by switching to the trityl protecting group. This synthetic protocol provides a convenient approach to many new largazole analogues. Three side chain analogues with multiple heteroatoms for chelation with Zn(2+) were synthesized, and their biological activities were evaluated. They were less potent than largazole 1 in growth inhibition of HCT116 colon carcinoma cell line and in inducing increases in global H3 acetylation. Largazole 1 and the three side chain analogues had no effect on HDAC6, as indicated by the lack of increased acetylation of α-tubulin.

publication date

  • 2011

published in

start page

  • 7453

end page

  • 63


  • 54