Xanthone analogs for treating infectious diseases and complexation of heme and porphyrins
AssigneeInterlab, Inc.
InventorsRolf W. Winter, Michael K. Riscoe, David J. Hinrichs
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Abstract
Therapeutic compounds and compositions for the treatment of infectious diseases are disclosed. The compounds are xanthones and xanthone derivatives, such as 3,5-bis-ε-(N,N-diethylamino)amyloxyxanthone. The described compositions include such compounds and a pharmaceutical carrier. These compositions also can include additional materials conventionally used to form therapeutic compositions. 3,5-bis-ε-(N,N-diethylamino)amyloxyxanthone has an IC50 for Plasmodium falciparum of about 0.15 μM, and an IC50 for Leishmania mexicana of <<0.5 μM. These compositions are additionally useful for forming soluble complexes with heme and porphyrins.
Claims31
A compound according to Formula X
- 57
- where A is oxygen, substituted antimony (stibium), sulfur or N-R′, where R′ is H, OH, alkyl, haloalkyl, aryl or haloaryl;
- R1-R8 are independently selected from the group consisting of H, OH, halogen, aryl, arylamine, alkyl, alkene, substituted alkyl, alkylthio, alkoxy, substituted alkoxy, cycloaminoalkoxy, substituted alkylthio, amino, amido, ester, ether and nitro groups and O-linked and C-linked carbohydrates;
- and Y is selected from the group consisting of NO, NOH, C═O, CH-OH, S═O, and SO2.
A composition comprising a pharmaceutical carrier and a compound having Formula X
- 58
- where A is oxygen, substituted antimony (stibium), sulfur or N-R′, where R′ is H, OH, alkyl, haloalkyl, aryl or haloaryl;
- R1-R8 are independently selected from the group consisting of H, OH, halogen, aryl, arylamine, alkyl, alkene, substituted alkyl, alkylthio, alkoxy, substituted alkoxy, cycloaminoalkoxy, substituted alkylthio, amino, amido, ester, ether and nitro groups and O-linked and C-linked carbohydrates;
- and Y is selected from the group consisting of NO, NOH, C═O, CH-OH, S═O, and SO2.
A method for inhibiting the growth of a microbial pathogen, comprising:
- providing a compound according to Formula X, or a composition comprising a compound according to Formula X
- 59
- where A is oxygen, substituted antimony (stibium), sulfur or N-R′, where R′ is H, OH, alkyl, haloalkyl, aryl or haloaryl;
- R1-R8 are independently selected from the group consisting of H, OH, halogen, aryl, arylamine, alkyl, alkene, substituted alkyl, alkylthio, alkoxy, substituted alkoxy, cycloaminoalkoxy, substituted alkylthio, amino, amido, ester, ether and nitro groups and O-linked and C-linked carbohydrates;
- and Y is selected from the group consisting of NO, NOH, C═O, CH-OH, S═O, and SO2;
- and
- contacting the pathogen with an effective amount of the compound or composition.
The method according to 19 where A is oxygen.
A compound having a structure
- X—Y—Z
- where X is a group capable of interacting with the iron atom in heme;
- Y is a planar aromatic system capable of interacting with the porphyrin ring;
- and Z is one or more groups capable of interacting with at least one carboxylate side group of heme.
A method for forming a soluble heme complex, comprising contacting heme with a compound having a structure
- X—Y—Z
- where X is a group capable of interacting with the iron atom in heme;
- Y is a planar aromatic system capable of interacting with the porphyrin ring;
- and Z is one or more groups capable of interacting with at least one carboxylate side group of heme.
A method for forming a soluble porphyrin complex, comprising contacting porphyrin with a compound having a structure
- X—Y—Z
- where X is a group capable of interacting with the iron atom in heme;
- Y is a planar aromatic system capable of interacting with the porphyrin ring;
- and Z is one or more groups capable of interacting with at least one carboxylate side group of heme.
Dependencies are inferred from the claim text.