1092363-40-0Relevant articles and documents
Largazole and analogues with modified metal-binding motifs targeting histone deacetylases: Synthesis and biological evaluation
Bhansali, Pravin,Hanigan, Christin L.,Casero, Robert A.,Tillekeratne, L. M. Viranga
, p. 7453 - 7463 (2012/01/03)
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 Zn2+ 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.