We describe herein the design and synthesis of N-phenyl phthalimide derivatives with inhibitory activities against Plasmodium falciparum (sensitive and resistant strains) in the low micromolar range and noticeable selectivity indices against human cells. The best inhibitor, 4-amino-2-(4-methoxyphenyl)isoindoline-1,3-dione (10), showed a slow-acting mechanism similar to that of atovaquone. Enzymatic assay indicated that 10 inhibited P. falciparum cytochrome bc₁ complex. Molecular docking studies suggested the binding mode of the best hit to Qo site of the cytochrome bc₁ complex. Our findings suggest that 10 is a promising candidate for hit-to-lead development.

This review aims to highlight microwave-assisted organic synthesis as applied to medicinal chemistry in the last years, showing some reactions performed under microwave irradiation for the synthesis of distinct structurally molecules of biological interest, divided into the following groups: antineoplastics, anti-inflammatory, antimicrobial agents, antivirals, agents for the treatment of neglected diseases and central nervous system-acting prototypes.