Synthesis and evaluation of the antimicrobial activity of novel quinazolinones

Abstract

A simple and efficient microwave-assisted methodology for regioselective alkylation of exocyclic nitrogen of cyclic amidines was developed and novel N-alkylated 3,4-dihydropyrazino[2,1-b]quinazolin-6-ones were prepared. Although none of the molecules tested have any specific anti-quorum sensing (–QS) activity, our result validates the growth tests devised to control the bias of the anti-QS tests. Among the molecules studied, compound 2b exhibits interesting activity against the Gram-negative bacteria Escherichia coli and Shigella sonnei.

Keywords::

• Quinazolinones
• microwave-assisted chemistry
• quorum sensing
• anti-microbial activity

Acknowledgements

We thank the “Comité de Charente-Maritime de la Ligue Nationale Contre le Cancer” and the “Conseil Général de la Charente Maritime” for financial support ((M.-F. P. and R. C. PhD grant respectively). We are indebted to Pr Michael Givskov (Technical University of Denmark) for providing the PA01 lasB-gfp(ASV) strain. We are grateful to Dr Denis Faure, (Institut des Sciences du Végétal CNRS Gif sur Yvette France) for providing the Chromobacterium and the Agrobacterium strains.