Antimalarial activity of synthetic analogues of distamycin

Malaria, one of the most serious diseases transmitted by arthropods, is largely present in tropical and even temperate zones in endemic or epidemic form. More than 40% of the world's population lives in areas at risk for exposure, and the World Health Organization reports that approximately 300 million people are affected by the infection (mostly caused by the species Plasmodium falciparum), with 1-2 million deaths per year. These data, and the fact that malaria is becoming increasingly refractory to treatment through resistance of the parasite to antimalarial agents currently in use, e.g., chloroquine, emphasize the need to develop new drugs. The well-known antiparasitic activity of oligopyrrolamidine natural products, such as distamycin and netropsin, suggested the antimalarial evaluation of related compounds obtained by new chemical modifications. Besides possessing antiviral and antitumoural properties, distamycin exhibits interesting in vitro activity against P. falciparum. Unfortunately, the high toxicity associated with this product precludes its development as a drug. However, some synthetic analogues of distamycin proved to be highly active against chloroquine-sensitive and -resistant strains of P. falciparum, besides showing low toxicity in vitro.