B-cyclodextrin derivatives and their use against anthrax lethal toxin
AssigneesPinnacle Pharmaceuticals, Inc., Innovative Biologics, Inc.
InventorsVLADIMIR KARGINOV, Sidney Hecht, Noureddine Fahmi, Ken Alibek
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Abstract
The invention provides low molecular weight compounds that block the pore formed by protective antigen and inhibit anthrax toxin action. Structures of the compounds are derivatives of β-cyclodextrin. Per-substituted alkylamino derivatives displayed inhibitory activity, and they were protective against anthrax lethal toxin action at low micromolar concentrations. Also, the addition of one of the alkylamino derivatives to the bilayer lipid membrane with multiple PA channels caused a significant decrease in membrane conductance. Thus, the invention also provides methods for protection against anthrax toxicity.
Claims11
1-3. (canceled)
A method for inhibiting anthrax toxicity in a cell, comprising contacting the cell with a compound according to the formula
- wherein R2 is H, OH, OAc, OMe, or O(CH2CH2O)n;
- R3 is H, OH, OAc, OMe, OSO3Na, or NH2;
- and R6 is H, NH2, SCH2CH2NH2, SCH2CH2CH2NH2, SCH2CH2CH2CH2NH2, I, N3, SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, aralkyl, aryl, heterocyclic ring(s), or OSO3Na.
The method according to claim 1, wherein R6 is NH2, SCH2CH2NH2, SCH2CH2CH2NH2, or SCH2CH2CH2CH2 NH2.
A method for inhibiting anthrax toxicity in a cell, comprising contacting the cell with a compound shown in FIG. 1.
(canceled)
A method for inhibiting anthrax toxin activity comprising administering a cyclic compound with a sevenfold symmetry and a diameter between 12 Å and 35 Å.
A method for inhibiting a virulence factor that is a protein forming a trans-membrane channel with sevenfold symmetry for α-toxin of S. aureus comprising contacting a cell with a compound according to the formula
- wherein R2 is H, OH, OAc, OMe, or O(CH2CH2O)n;
- R3 is H, OH, OAc, OMe, OSO3Na, or NH2;
- and R6 is H, NH2, SCH2CH2NH2, SCH2CH2CH2NH2, SCH2CH2CH2CH2NH2, I, N3, SH, lower alkyl, S-alkylguanidyl, O-alkylguanidyl, S-aminoalkyl, O-aminoalkyl, aminoalkyl, aralkyl, aryl, heterocyclic ring(s), or OSO3Na.
A method for inhibiting a virulence factor that is a protein forming a trans-membrane channel with sevenfold symmetry for α-toxin of S. aureus comprising contacting a cell with a compound shown in FIG. 1.
A method for inhibiting a virulence factor that is a protein forming a trans-membrane channel with sixfold symmetry for Heliobacter pylori Vac A toxin comprising contacting a cell with a derivative of hexameric β-cyclodextrin.
A method for inhibiting a virulence factor that is a protein forming a trans-membrane channel with sixfold symmetry for Hepatitis C virus p7 protein comprising contacting a cell with a derivative of hexameric β-cyclodextrin.
Dependencies are inferred from the claim text.