Scaffold and Parasite Hopping: Discovery of New Protozoal Proliferation Inhibitors
Baljinder Singh, Jean Bernatchez, Laura‐Isobel McCall, Cláudia M. Calvet, Jasmin Ackermann, Jorge Augusto Soares de Souza, Diane Thomas, Everton M. Silva, Kelly A. Bachovchin, Dana M. Klug, Hitesh B. Jalani, Seema Bag, Melissa J. Buskes, Susan E. Leed, Norma Roncal, Erica Penn, Jessey Erath, Ana Rodrı́guez, Richard J. Sciotti, Robert F. Campbell, James H. McKerrow, Jair L. Siqueira-Neto, Lori Ferrins, Michael P. Pollastri
Abstract
Utilizing a target repurposing and parasite-hopping approach, we tested a previously reported library of compounds that were active against Trypanosoma brucei, plus 31 new compounds, against a variety of protozoan parasites including Trypanosoma cruzi, Leishmania major, Leishmania donovani, and Plasmodium falciparum. This led to the discovery of several compounds with submicromolar activities and improved physicochemical properties that are early leads toward the development of chemotherapeutic agents against kinetoplastid diseases and malaria.