β-Cyclodextrin derivatives that inhibit anthrax lethal toxin

Recently, we demonstrated that simultaneous blocking of bacteria] growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using beta-cyclodextrin as the starting molecule. Several beta-cycloclextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low microinolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates For anthrax treatment. (c) 2005 Elsevier Ltd. All rights reserved.