Patent number 6,589,966
July 8, 2003
Cytotoxic Metal Chelators and methods for making and using same
A family of hexadentate Fe(II) chelators having marked antiproliferative activity against tumor cells is disclosed. The cytotoxic metal chelators and complexes of the present invention are represented by the general formula below: ##STR1## wherein: X.sup.1, X.sup.3, and X.sup.5 are N, O or S, wherein the X.sup.1, X.sup.3, and X.sup.5 atoms are at the 1, 3, and 5 positions of a cyclohexyl group and are in a cis, cis disposition; B, B', and B" are aliphatic, branched aliphatic, or aryl groups, or any combination thereof, wherein the number of atoms between X and Y is about 2 to about 4; Y, Y' and Y" contain N, O, or S atoms that originate from either aliphatic, branched aliphatic, aryl, or heterocyclic groups, or any combination thereof, and/or Y, Y' and Y" are NH.sub.2 or NHR, OH, or SH, CO.sub.2 H, P(O)(OH).sub.2, RP(O)OH, ROP(O)OH groups or a combination thereof, and R is H, aliphatic, branched aliphatic, or aryl groups, or any combination thereof that may or may not be identical in Y, Y' and Y"; s, s', and s" are 0 to about 2; and t, t', and t" are 0 to about 2. Application of the metal chelators of the present invention as chemotherapeutic agents is also disclosed.