Michael Brand, Lei Wang, Stefano Agnello, Silvia Gazzola, Flavio M Gall, Luka Raguž, Marcel Kaiser, Remo S Schmidt, Amélie Ritschl, Jennifer Jelk, Andrew Hemphill, Pascal Mäser, Peter Bütikofer, Michael Adams, Rainer Riedl
Leucinostatin A is one of the most potent antiprotozoal compounds ever described, but little was known on structure-activity relationships (SAR). We used Trypanosoma brucei as a protozoal model organism to test synthetically modified derivatives, resulting in simplified but equally active compounds 2 (ZHAWOC6025) and 4 (ZHAWOC6027), which were subsequently modified in all regions of the molecule to gain an in-depth SAR understanding. The antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity, leaking, and dynamics were studied...
March 17, 2021: Angewandte Chemie