Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria.

Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure-activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth.

Tolevamer, an anionic polymer, neutralizes toxins produced by the BI/027 strains of Clostridium difficile.

Clostridium difficile-associated diarrhea (CDAD) is caused by the toxins the organism produces when it overgrows in the colon as a consequence of antibiotic depletion of normal flora. Conventional antibiotic treatment of CDAD increases the likelihood of recurrent disease by again suppressing normal bacterial flora. Tolevamer, a novel toxin-binding polymer, was developed to ameliorate the disease without adversely affecting normal flora.