Substituted Fullerenes and Their Use as Inhibitors of Cell Death
First Claim
Patent Images
1. A method of inhibiting cell death, comprising:
- administering to a mammal an effective amount of a composition comprising a substituted fullerene, wherein the substituted fullerene comprises a fullerene core (Cn), whereinn is an even integer greater than or equal to 60, and at least one of i-iv;
(i) m (>
CX1X2) groups bonded to the fullerene core, wherein;
(i-a) m is an integer from 1 to 6, inclusive,(i-b) each X1 and X2 is independently selected from —
H;
—
COOH;
—
CONH2;
—
CONHR′
;
—
CONR′
2;
—
COOR′
;
—
CHO;
—
(CH2)dOR11;
a peptidyl moiety;
—
R;
—
RCOOH;
—
RCONH2;
—
RCONHR′
;
—
RCONR′
2;
—
RCOOR′
;
—
RCHO;
—
R(CH2)dOR11;
a heterocyclic moiety;
a branched moiety comprising one or more terminal —
OH, —
NH2, triazole, tetrazole, or sugar groups;
or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′
is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20, and each R11 is independently —
H, a charged moiety, or a polar moiety;
(ii) p —
X3 groups bonded to the fullerene core, wherein;
(ii-a) p is an integer from 1 to 18, inclusive; and
(ii-b) each —
X3 is independently selected from —
N+(R2)(R3)(R4), wherein R2, R3, and R4 are independently —
H or —
(CH2)d—
CH3, wherein d is an integer from 0 to about 20;
—
N+(R2)(R3)(R4), wherein R2 and R3 are independently —
H or —
(CH2)d—
CH3, wherein d is an integer from 0 to about 20, and each R8 is independently —
(CH2)fSO3−
, —
(CH2)fPO4−
, or —
(CH2)fCOO−
, wherein f is an integer from 1 to about 20;
—
C(R5)(R6)(R7), wherein R5, R6, and R7 are independently —
COOH, —
H, —
CH(═
O), —
CH2OH, or a peptidyl moiety;
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Abstract
This patent discloses the use of water-soluble substituted fullerenes as inhibitors of cell death. The substituted fullerenes comprise a fullerene core (Cn) and at least one of: (i) from 1 to 6 (>CX1X2) groups bonded to the fullerene core; (ii) from 1 to 18 —X3 groups bonded to the fullerene core; (iii) from 1 to 6 —X4— groups bonded to the fullerene core; or (iv) from 1 to 6 dendrons bonded to the fullerene core.
19 Citations
16 Claims
-
1. A method of inhibiting cell death, comprising:
-
administering to a mammal an effective amount of a composition comprising a substituted fullerene, wherein the substituted fullerene comprises a fullerene core (Cn), wherein n is an even integer greater than or equal to 60, and at least one of i-iv; (i) m (>
CX1X2) groups bonded to the fullerene core, wherein;(i-a) m is an integer from 1 to 6, inclusive, (i-b) each X1 and X2 is independently selected from —
H;
—
COOH;
—
CONH2;
—
CONHR′
;
—
CONR′
2;
—
COOR′
;
—
CHO;
—
(CH2)dOR11;
a peptidyl moiety;
—
R;
—
RCOOH;
—
RCONH2;
—
RCONHR′
;
—
RCONR′
2;
—
RCOOR′
;
—
RCHO;
—
R(CH2)dOR11;
a heterocyclic moiety;
a branched moiety comprising one or more terminal —
OH, —
NH2, triazole, tetrazole, or sugar groups;
or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′
is independently a hydrocarbon moiety having from 1 to about 6 carbon atoms, an aryl-containing moiety having from 6 to about 18 carbon atoms, a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20, and each R11 is independently —
H, a charged moiety, or a polar moiety;(ii) p —
X3 groups bonded to the fullerene core, wherein;(ii-a) p is an integer from 1 to 18, inclusive; and (ii-b) each —
X3 is independently selected from —
N+(R2)(R3)(R4), wherein R2, R3, and R4 are independently —
H or —
(CH2)d—
CH3, wherein d is an integer from 0 to about 20;—
N+(R2)(R3)(R4), wherein R2 and R3 are independently —
H or —
(CH2)d—
CH3, wherein d is an integer from 0 to about 20, and each R8 is independently —
(CH2)fSO3−
, —
(CH2)fPO4−
, or —
(CH2)fCOO−
, wherein f is an integer from 1 to about 20;
—
C(R5)(R6)(R7), wherein R5, R6, and R7 are independently —
COOH, —
H, —
CH(═
O), —
CH2OH, or a peptidyl moiety; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
-
-
10. A method of inhibiting cell death, comprising:
administering to a mammal an effective amount of a composition comprising a substituted fullerene selected from the group consisting of C3 and DF-1, wherein the mammal suffers or is susceptible to cell death caused by a toxin selected from the group consisting of doxorubicin, cisplatin, 5-fluorouracil, or TNF. - View Dependent Claims (11, 12, 13, 14, 15, 16)
Specification