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...

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Published in:ChemistrySelect (Weinheim) 2020-05, Vol.5 (20), p.5965-5969
Main Authors: Rasapalli, Sivappa, Reddy Sammeta, Vamshikrishna, Singh, Sarbjit, Golen, James A., Semerdzhiev, Dimitar, Bo, Yang, Silby, Mark, Rao, Reeta, Ali, Akbar, Schiffer, Celia A., Savinov, Sergey N.
Format: Article
Language:English
Subjects:
acyl aminoimidazole
anti-biofilm
Cell adhesion
Heterocycles
Imidazopyrimidine
Oroidin
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Summary: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. A series of 4/5‐aroyl‐2‐aminoimidazoles were synthesized and evaluated for their efficiency in inhibiting the bacterial biofilm formation. The in‐vitro activity results and cheminformatic analysis revealed importance of 2‐aminoimidazole's pKa and its protonation propensity as the key factors for the activity. The library was also tested for fungal cell adhesion inhibition and revealed that appending dibromomaleimide is beneficial for the activity.
ISSN:2365-6549
2365-6549
DOI:10.1002/slct.202001302