Synthesis of Apicidin-Derived Quinolone Derivatives:  Parasite-Selective Histone Deacetylase Inhibitors and Antiproliferative Agents

Apicidin's indole was efficiently converted into a series of N-substituted quinolone derivatives by indole N-alkylation followed by a two-step, one-pot, ozonolysis/aldol condensation protocol. The new quinolones exhibited good parasite selectivity and potency both at the level of their molecular target, histone deacetylase, and in their whole cell antiproliferative activity in vitro.