Synthesis and biological evaluation of new N-acyl-homoserine-lactone analogues, based on triazole and tetrazole scaffolds, acting as LuxR-dependent quorum sensing modulators.

Mohamad Sabbah (1) , Fanny Fontaine , Lucie Grand (1) , Mohamed Boukraa , Mohamed L Efrit , Alain Doutheau (1) , Laurent Soulère (1) , Yves Queneau (1)

1 COB - Chimie Organique et Bioorganique

New analogues of N-acyl-homoserine-lactone (AHL), in which the amide was replaced by a triazole or tetrazole ring, were prepared and tested for their activity as LuxR-dependent QS modulators. Several compounds showed a level of antagonistic or agonistic activity, notably some 1,4-triazolic and 1,5-tetrazolic derivatives, whereas the 2,5-tetrazolic compounds were inactive. In 1,5-tetrazoles, substituted with butyrolactone and an alkyl chain, the activity was reversed, depending on the connection between the lactone and the tetrazole. The C-N connected compounds were agonists whereas the C-C connected ones were antagonists.

Domaines: Chimie organique

Mohamad Sabbah, Fanny Fontaine, Lucie Grand, Mohamed Boukraa, Mohamed L Efrit, et al.. Synthesis and biological evaluation of new N-acyl-homoserine-lactone analogues, based on triazole and tetrazole scaffolds, acting as LuxR-dependent quorum sensing modulators.. Bioorganic and Medicinal Chemistry, 2012, 20 (15), pp.4727-36. ⟨10.1016/j.bmc.2012.06.007⟩. ⟨hal-00919262⟩