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Very recently the research group of Melander has been studying widely the ability of
simple analogues of the marine natural products bromoageliferin and oroidin (Fig.
1.11.6) to control biofilm development. Bromoageliferin is a sponge-derived alkaloid
that was reported to inhibit the formation of bacterial biofilms from marine sources,
presumably as a defense mechanism against biofouling. 117 They reasoned that core
structures derived from this complex molecule could be used as structural inspiration
for the development of potent and synthetically accessible anti-biofilm agents. One of
these scaffolds developed was based upon an aryl framework. 118 From a medicinal
chemistry stand point, this scaffold was deemed a promising platform to develop
further functionalized 2-aminoimidazole (2-AI) derivatives as diversity could rapidly
be introduced through manipulation of the benzene ring. They described the synthesis
and anti-biofilm activity of these aryl 2-AI derivatives against three commonlystudied
Gram-negative bacteria.
H 2N
H 2N
N
N
H
N
Bromoageliferin
NH
HN
Br
N
H
O
O
NH
H
N
Br
Br
H 2N
N
N
H
H 2N
Fig. 1.11.6 2-Aminoimidazole-based anti-biofilm molecules.
N
H
O
Oroidin
N
N
H
H
N
Br
R
Aryl 2-AI scaffold
The research group of melander has recently developed several novel libraries of 2-
aminoimidazole small molecules inspired by the marine alkaloids bromoageliferin
and oroidin. These natural products were reviously reported to inhibit biofilm
formation of the marine arotobacterium Rhodospirillum salexigens. 119 TAGE and
CAGE were the first documented 2-aminoimidazoles with anti-biofilm activity against
Pseudomonas aeruginosa biofilms.
Analogues of the structurally simpler alkaloid oroidin were also pursued to develop
novel classes of small molecules with anti-biofilm activity. Recently, an oroidin
Br