APICIDIN - A NOVEL ANTIPROTOZOAL AGENT THAT INHIBITS PARASITE HISTONEDEACETYLASE

A novel fungal metabolite, apicidin oleucinyl-D-pipecolinyl-L-2-amino- 8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal ac tivity in vitro against Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium ber ghei malaria in mice. Many Apicomplexan parasites cause serious, life- threatening human and animal diseases, such as malaria, cryptosporidio sis, toxoplasmosis, and coccidiosis, and new therapeutic agents are ur gently needed. Apicidin's antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), wh ich induces hyperacetylation of histones in treated parasites. The ace tylation-deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells, Other known HDA inhib itors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of no vel antiparasitic agents.