In this paper we describe the design and synthesis of 18 derivatives of the antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester and ether functions. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. All the compounds showed potent activity, with IC(50) values in the range of 1.25-50 nM, comparable to those of atovaquone and much higher than chloroquine or quinine.