Synthesis and Biological Evaluation of 4/5-Aroyl-2-aminoimidazoles as Microbial Biofilm Inhibitors

We had earlier used Oroidin, a 2-aminoimidazole-pyrrole natural microbial biofilm inhibitor, as a structural prototype to develop its 4/5-acyl modified form as an anti-biofilm lead for further optimization. Herein, as a part of our efforts towards that direction, we report the design, synthesis, as well as anti-bacterial, anti-biofilm, and fungal adhesion inhibition activities of various 4/5-aroyl-2-aminoimidazoles. These simplified Oroidin analogues are moderately active against bacterial biofilms and attest to the need for an aliphatic acyl linker that was part of the original 4/5-acyl modified Oroidin lead. From our studies, protonation propensity of the 2-aminoimidazole group of the series emerges as an important pre-requisite for potent antibiofilm activity. Also, the fungal biofilm screening studies identified analogue 8 b as an active molecule.