(Thio, oxo and seleno) semicarbazone complexes with zinc and their use for treating cancer
The invention provides organic complexes of Zn 2+ that are useful for treating cancer, as well as compositions and kits comprising such complexes, and intermediate monomer compounds that are useful for the preparation of such complexes.
1. A complex comprising Zn 2+ and a compound of formula (I):
or an ion or poly-ion thereof; or a solvate thereof, wherein:
n is 0, 1, 2, 3, or 4;
Y is O, S, or Se;
each R 1 is independently selected from (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, and halo;
R 2 is selected from the group consisting of H and (C 1 -C 6 )alkyl that is optionally substituted with aryl; and
R a and each R b are each independently selected from H, (C 1 -C 6 )alkyl, aryl, and aryl(C 1 -C 6 )alkyl; wherein the ratio of the number of compounds of formula (I) or ions or poly-ions thereof or solvates thereof to zinc Zn 2+ ions is about 2:1; provided the compound is not:
2. The complex of claim 1 wherein:
n is 0;
R 2 is (C 1 -C 4 )alkyl;
Y is S or Se; and
R a and each R b are each independently selected from H and (C 1 -C 6 )alkyl;
or a solvate thereof.
3. The complex of claim 1 that comprises a compound selected from the group consisting of:
and ions and poly-ions thereof; and solvates thereof.
4. The complex or of claim 1 , wherein R a is selected from (C 1 -C 6 )alkyl, aryl, and aryl(C 1 -C 6 )alkyl; or a solvate thereof.
5. The complex of claim 1 , wherein R a and each R b are each independently selected from (C 1 -C 6 )alkyl, aryl, and aryl(C 1 -C 6 )alkyl; or a solvate thereof.
6. A pharmaceutical composition, comprising a complex of claim 1 , or a solvate thereof, and a pharmaceutically acceptable carrier.
7. An injectable pharmaceutical formulation comprising, a complex of claim 1 , or a solvate thereof, and a pharmaceutically acceptable carrier.