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-po t, ozonolysis/aldol condensation protocol. The new quinolones exhibited goo d parasite selectivity and potency both at the level of their molecular tar get, histone deacetylase, and in their whole cell antiproliferative activit y in vitro.