In silico design and synthesis of piperazine-1-pyrrolidine-2,5-dione scaffold-based novel malic enzyme inhibitors

Fragment-based virtual library design and virtual screening have been conducted against malic enzyme (ME) homology model. Several scaffolds have been identified as promising motifs to target ME’s NADP binding site. One small focused library has been synthesized and tested against ME. Several compounds from this library have shown sub-micromolar inhibitory activity against malic enzyme.