Phenylahistin and the phenylahistin analogs, a new class of anti-tumor compounds
Methods of using a compound, its pharmaceutically acceptable salts, and/or its pro-drug esters, in isolated form, to treat cancer, and methods for isolating, for formulating, and for administering the compound, salt, and/or pro-drug ester as an antitumor agent, wherein the compound, salt, or pro-drug ester has the following structure: wherein: R 1 , R 2 , R 5 , R 7 , and R 8 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 1 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups, R 3 , R 4 , and R 6 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12 alkyl, unsaturated C 1 -C 12 alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups, X 1 and X 2 are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond. Most preferably, R 3 and R 4 are hydrogen, and each are involved in hydrogen bonds, and/or the dashed bond is a double bond, such that the chemical backbone of the compound substantially retains a substantially planar conformation.
1 . A method of preventing at least one fungal infection in a mammal afflicted with at least one fungal infection which comprises administering an antifungally effective amount of a compound sufficient for such treating or preventing, and wherein the compound has the following structure:
wherein:
R 1 , R 2 , R 5 , R 7 , and R 8 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 1 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups,
R 3 , R 4 , and R 6 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12 alkyl, unsaturated C 1 -C 12 alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups,
X 1 and X 2 are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and
the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond.
2 . The method of claim 1 , wherein the fungal infection is selected from the group consisting of an Aspergillosis infection, blastomycosis infection, Candidiasis infection, Coccidioidomycosis infection, Cryptococcosis infection, Histopolasmosis infection, Paracoccidioidomycosis, Sporotrichosisand, and Mucormycosis infection.
3 . The method of claim 2 , wherein the Aspergillosis infection is invasive pulmonary aspergillosis.
4 . The method of claim 2 , wherein the Mucormycosis infection is craniofacial mucormycosis or pulmonary mucormycosis.
5 . The method of claim 2 , wherein the Candidiasis infection is retrograde candidiasis of the urinary tract.
6 . A pharmaceutical composition for preventing fungal infection comprising an antifungally effective amount of a pharmaceutically acceptable carrier and a compound having the structure:
wherein:
R 1 , R 2 , R 5 , R 7 , and R 8 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 1 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups,
R 3 , R 4 , and R 6 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12 alkyl, unsaturated C 1 -C 12 alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups,
X 1 and X 2 are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and
the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond.
7 . The composition of claim 6 , wherein the fungal infection is selected from the group consisting of an Aspergillosis infection, blastomycosis infection, Candidiasis infection, Coccidioidomycosis infection, Cryptococcosis infection, Histopolasmosis infection, Paracoccidioidomycosis, Sporotrichosisand, and Mucormycosis infection.
8 . The composition of claim 7 , wherein the Aspergillosis infection is invasive pulmonary aspergillosis.
9 . The composition of claim 7 , wherein the Mucormycosis infection is craniofacial mucormycosis or pulmonary mucormycosis.
10 . The composition of claim 7 , wherein the Candidiasis infection is retrograde candidiasis of the urinary tract.