A ChemoEnzymatic Approach for the Preparation of “Linear-Shaped” Diaryl Pyrazines as Potential Antiprotozoal Agents

Nitrogenous heterocyclic rings are present in a wide range of drugs, natural compounds, and fine chemicals and are considered privileged scaffolds in medicinal chemistry. Seeking novel anti-protozoal drugs acting on new targets or by novel mechanisms of action, we focused on a preliminary evaluation of the potential of "linear-shaped" diaryl pyrazines. To this purpose, a two-enzyme chemoenzymatic synthesis of this heteroaromatic core was carried out. Specifically, starting from simple, commercially available aromatic aldehydes, the target pyrazines were obtained through a sequence of biocatalytic benzoin condensation, chemical oxidation and a transaminase-mediated tandem process of transamination and cyclization. The profiles of the compounds as antiprotozoal agents were evaluated in vitro against parasites cultures of the Leishmania and Plasmodium genera and using the human cell line HepG2.Starting from simple, commercially available aromatic aldehydes, "linear-shaped" diaryl pyrazines were prepared by a novel chemoenzymatic route comprising a biocatalyzed benzoin condensation reaction and a transaminase-mediated tandem process of transamination and cyclization. The obtained pyrazines were tested for their potential leishmanicidal and antiplasmodial activity in vitro. image