Cyclodextrin derivatives as anti-infectives

• Cyclodextrins derivatives block pore-forming toxins and inhibit bacterial infection.
• The symmetry match of blockers and target pores improved the selection of potent inhibitors.
• Multi-targeted inhibitors were identified that could be developed into broad-spectrum drugs.
• This approach can be used to find new drugs against pathogens producing pore-forming proteins.

Cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. The highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. Inhibitors of several bacterial toxins produced by Bacillus anthracis, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum, and Clostridium difficile were identified from a library of ∼200 CD derivatives. It was demonstrated that multi-targeted inhibitors can be found using this approach and could be utilized for the development of broad-spectrum drugs against various pathogens.

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