Medium-Ring Keto Bislactams with Antischistosomal Activity

Abstract

We discovered medium-ring keto bislactams as a new antischistosomal chemotype. The ketone functional group and isoindolinone substructure were required for high antischistosomal activity. Aryl substitution with EWG functional groups decreased the chemical stability. These compounds were relatively polar with the measured LogD_7.4 values ranging from <0 to 2.4, had kinetic aqueous solubilities between 40 and >320 μM, and had relatively low cytotoxicities with IC_50s ranging from 52 to >390 μM. We identified two compounds with IC₅₀ values < 5 μM against ex vivoSchistosoma mansoni (S. mansoni).