TY - JOUR
T1 - β-Cyclodextrin derivatives that inhibit anthrax lethal toxin
AU - Karginov, Vladimir A.
AU - Yohannes, Adiamseged
AU - Robinson, Tanisha M.
AU - Fahmi, Nour Eddine
AU - Alibek, Kenneth
AU - Hecht, Sidney M.
N1 - Funding Information:
The authors thank S. Bezrukov and E. Nestorovich for the ion conductance data and G. Vigh for the sulfo β-cyclodextrin derivatives. This work was supported by Grant 1R43AI052894-01 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - Recently, we demonstrated that simultaneous blocking of bacterial 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 β-cyclodextrin as the starting molecule. Several β-cyclodextrin 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 micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment.
AB - Recently, we demonstrated that simultaneous blocking of bacterial 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 β-cyclodextrin as the starting molecule. Several β-cyclodextrin 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 micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment.
KW - Anthrax treatment
KW - Lethal toxin inhibitors
KW - β-Cyclodextrin derivatives
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U2 - 10.1016/j.bmc.2005.07.054
DO - 10.1016/j.bmc.2005.07.054
M3 - Article
C2 - 16169738
AN - SCOPUS:27744524135
SN - 0968-0896
VL - 14
SP - 33
EP - 40
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -