Synthesis and trypanocidal activity of the bis-carba analogue of pentamidine

Abstract

Because toxic metabolites are formed by microsomal oxidative cleavage of the ether methylenes of the antiprotozoal drug, pentamidine, we synthesized the previously unreported analogue of pentamidine in which the ether oxygens are replaced by methylenes. Although this compound was about 20-fold less active than pentamidine against Trypanosoma brucei infection in mice, it did not undergo oxidative cleavage, suggesting a new direction for design of less toxic pentamidine analogues.