Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents

To date, the use of corannulene has
been restricted in the area
of material science, but its application in biomedical research has
yet to be established due to its nonsolubility in an aqueous environment
and synthetic infeasibility. Herein, we detail the development of
a new family of highly curved π-conjugated corannulene-containing
unnatural α-amino acid (CAA) derivatives to overcome this challenge.
These CAAs have been extended as novel constituents for the synthesis
of corannulene-containing water-soluble cationic peptides (CCPs),
which display inhibitory activity against broad-spectrum pathogenic
bacteria along with drug-resistant bacteria via a membrane-damaging
mechanism. Importantly, several of the synthesized peptides were found
to be appreciably nonhemolytic against hRBCs and noncytotoxic against
mammalian 3T3 cells. In vivo efficacy studies of
the potent and least cytotoxic peptide 6a demonstrated
clearance of bacteria from the spleen, liver, lung, and blood of mice
infected with S. aureus ATCC 25923.