Synthesis of new pyrido-benzodiazepine salts and their antimicrobial activities

Abstract

Recently, we reported the antiprotozoal activity of tetrahydropyridylidene ammonium salts. We inserted this motif into a fused ring system, a pyrido-benzodiazepine. The synthesis includes an enamine formation followed by a Mannich reaction to cyclic products and an S-methylation. The last step is a regioselective reduction process. All new compounds were characterized by UV–Vis spectroscopy, ATR FTIR spectroscopy, and HRMS as well as NMR spectroscopy. The structures of the reduction products were established using a single X-ray structure analysis. The new compounds were investigated for their antitrypanosomal and antiplasmodial activities as well as for their cytotoxicity using microplate assays. Furthermore, their inhibitory properties against Mycobacterium smegmatis were determined using a microbroth dilution assay. The potencies against some Gram-positive and Gram-negative bacteria as well as against yeasts were detected using an agar diffusion assay. Structure–activity relationships are discussed.