Compositions, methods, and kits comprising platinum compounds associated with a ligand comprising a targeting moiety
Compositions, kits, and methods for treatment of cancers are generally provided. In some embodiments, the compositions, kits, and methods comprise a platinum (e.g., Pt(II) or Pt(IV)) compound associated with a ligand (e.g., a beta-diketonate ligand) comprising a targeting moiety. Methods of synthesizing platinum (e.g., Pt(II) or Pt(IV)) compounds associated with a ligand comprising a targeting moiety are also provided.
1. A compound having the structure:
wherein:
R 1 is selected from the group consisting of alkyl optionally substituted, heteroalkyl optionally substituted, and aryl optionally substituted;
R 2 is a targeting moiety, wherein R 2 is a protein, a peptide, a nucleic acid, a nucleic acid analog, a carbohydrate, or a small molecule;
R 3 and R 4 are independently selected from the group consisting of ammonia, an optionally substituted heterocycle including at least one nitrogen, and an optionally substituted amine, or R 3 and R 4 can be joined together to form a bidentate ligand;
R 5 and R 6 are independently selected from the group consisting of hydroxyl, alkoxy, aryloxy, and acyloxy, each optionally substituted;
L is a linking group;
Z and Y are independently selected from the group consisting of O and S; and
X − is a counterion.
2. The compound of claim 1 , wherein L comprises the structure —(CH 2 )—(C═O)—, —(CH 2 ) n (C═O)NH—, —[(CH 2 ) m O] n (C═O)—, or —[(CH 2 ) m O] n (C═O)NH—, wherein n is an integer.
3. The compound of claim 1 , wherein at least one of R 3 and R 4 is NH 3 .
4. The compound of claim 1 , wherein each of R 3 and R 4 is NH 3 .
5. The compound of claim 1 , wherein R 3 and R 4 are independently selected from the group consisting of ammonia and an optionally substituted amine, and are not joined together to form a bidentate ligand.
6. The compound of claim 1 , wherein Z is O and Y is S.
7. The compound of claim 1 , wherein Z is S and Y is O.
8. The compound of claim 1 , wherein each of Z and Y is O.
9. The compound of claim 1 , wherein each of Z and Y is S.
10. A method for treating a subject having a cancer, comprising:
administering a therapeutically-effective amount of a compound as in claim 5 to a subject having a cancer.
11. A method, comprising:
promoting the inhibition or treatment of a cancer in a subject susceptible to or exhibiting symptoms of a cancer via administration to the patient of a composition comprising a compound as in claim 1 .
12. A kit for treatment of a cancer, comprising:
a composition comprising a compound as in claim 1 ; and
instructions for use of the composition for treatment of a cancer.
13. A pharmaceutical composition, comprising:
a compound as in claim 1 ; and
one or more pharmaceutically acceptable carriers, additives, and/or diluents.
14. The compound of claim 1 , wherein the peptide comprises a cell-penetrating peptide or a mitochondria-penetrating peptide.
15. The compound of claim 14 , wherein the cell-penetrating peptide is one or more of Tat peptide, oligoarginine (r9), oligolysine (k9), and penetratin.
16. The compound of claim 14 , wherein the mitochondria-penetrating peptide is one or more of (F x r) b wherein F X and r are cyclohexylalanine and d-arginine, respectively, and b is an integer greater than 1.
17. The compound of claim 1 , wherein the targeting moiety comprises a label.
18. The compound of claim 17 , wherein the label is a fluorescent label.
19. The compound of claim 1 , wherein the targeting moiety comprises a terminating group.
20. The compound of claim 1 , wherein the compound has the structure:
21. A compound having the structure:
wherein:
R 1 is selected from the group consisting of alkyl optionally substituted, heteroalkyl optionally substituted, and aryl optionally substituted;
R 2 is a targeting moiety;
R 3 and R 4 are independently selected from the group consisting of ammonia, an optionally substituted heterocycle including at least one nitrogen, and an optionally substituted amine, or R 3 and R 4 can be joined together to form a bidentate ligand;
R 5 and R 6 are independently selected from the group consisting of hydroxyl, alkoxy, aryloxy, and acyloxy, each optionally substituted;
L comprises the structure —(CH 2 ) n (C═O)—, —(CH 2 ) n (C═O)NH—, —[(CH 2 ) m O] n (C═O)— or —[(CH 2 ) m O] n (C═O)NH—, wherein each m and n is an integer;
Z and Y are independently selected from the group consisting of O and S; and
X − is a counterion.
22. The compound of claim 21 , wherein R 2 comprises at least one of a protein, a peptide, a nucleic acid, a nucleic acid analog, a carbohydrate, a small molecule, an antibody, a nanoparticle, a sugar, and a polymer.
23. The compound of claim 22 , wherein the targeting moiety comprises a label or a terminating group.
24. A method, comprising:
promoting the inhibition or treatment of a cancer in a subject susceptible to or exhibiting symptoms of a cancer via administration to the patient of a composition comprising a compound as in claim 21 .
25. The compound of claim 1 , wherein the targeting moiety comprises a label or a terminating group.
26. A compound having the structure:
wherein:
R 1 is selected from the group consisting of alkyl optionally substituted, heteroalkyl optionally substituted, and aryl optionally substituted;
R 2 is a targeting moiety;
R 3 and R 4 are independently selected from the group consisting of ammonia, an optionally substituted heterocycle including at least one nitrogen, and an optionally substituted amine, or R 3 and R 4 can be joined together to form a bidentate ligand;
R 5 and R 6 are independently selected from the group consisting of hydroxyl, alkoxy, aryloxy, and acyloxy, each optionally substituted;
L is a linking group;
Z and Y are independently selected from the group consisting of O and S, wherein Z is O and Y is S or wherein Z is S and Y is O; and
X − is a counterion.
27. The compound of claim 26 , wherein R 2 comprises at least one of a protein, a peptide, a nucleic acid, a nucleic acid analog, a carbohydrate, a small molecule, an antibody, a nanoparticle, a sugar, and a polymer.
28. The compound of claim 26 , wherein the targeting moiety comprises a label or a terminating group.
29. A method, comprising:
promoting the inhibition or treatment of a cancer in a subject susceptible to or exhibiting symptoms of a cancer via administration to the patient of a composition comprising a compound as in claim 26 .