Synthesis of nitric oxide releasing conjugated ortho-hindered nitroarenes and their application in dual-action antimicrobial peptide-mimics.
Attard Samuel T ST, Aquib Md M, Gmedhin Hatu H, Boyer Cyrille C et al.
This study reports the synthesis of a range of novel peptide-mimicking antimicrobials with conjugated ortho-hindered nitroarenes (CONAs) for nitric oxide release. These peptide-mimics were rationally designed, building from a previously established anthranilamide peptide-mimicking scaffold and synergistically substituting aromatic capping groups for aromatic CONAs. CONAs were synthesised via a novel synthetic pathway, avoiding the use of highly toxic CrO3 and red fuming nitric acid, in fewer steps and good-excellent yields compared to previously reported methods. Of the synthesised peptide-mimics, one formed a self-assembling low molecular weight hydrogel, and their gel properties were characterised by rheology, atomic force microscopy and circular dichroism. The synthesised compounds released NO when exposed to 530 nm light, and their antimicrobial activity was measured via a minimum inhibitory concentration assay, with one compound exhibiting activity against Gram-positive Staphylococcus aureus at 8 µg mL-1.