The M1 aminopeptidases catalyze the cleavage of amino acids from the N-terminus of proteins or peptides. They belong to the sub family MA (E) and are also known as Glu-zincins with one essential catalytic zinc ion in the active site. M1 aminopeptidases are widely distributed in animal cells, plants, bacteria, parasites and fungi. These enzymes play important biological roles (e.g. angiotensin system, immune system, and in inflammation) and are involved in many associated diseases[1],[2]. Our research group has previously reported the development of potent and selective inhibitors of APN/CD13. This allowed us to identify aminobenzosuberone core as a promising scaffold that demonstrates an exceptional selectivity towards the M1 aminopeptidase family.

In this work we focus on the development of potent and selective inhibitors of Pfa-M1. This M1 aminopeptidase plays a major role in plasmodium life cycle[3], [4]; it is involved in the last step of hemoglobin breakdown by hydrolyzing dipeptides into essential amino-acids[5].

Hereby, we present our most recent advances in the syntheses of the aminobenzosuberone analogues, SAR studies, 3D structures as well as pharmacological and pharmacokinetic data.