2-Acylamino-5-chlorobenzophenones with enhanced selectivity towards malaria parasites

Previously we described a series of 5-acylaminobenzophenones with considerable antimalarial activity. Unfortunately, most compounds also displayed high cytotoxicity resulting in low selectivity towards malaria parasites. Through the replacement of the 5-acylamino moiety by simple chlorine and further modifications of the 2-acylamino residue we could obtain inhibitors with improved selectivity towards malaria parasites combined with an acceptable reduction of antimalarial activity.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Extensive SAR regarding antimalarial activity of benzophenone derivatives were established. ► Due to enhanced antimalarial activity and lower cytotoxicity selectivity was enhanced. ► Compounds are readily accessable in few synthetic steps.