Gadolinium texaphyrin-methotrexate conjugates. Towards improved cancer chemotherapeutic agents.

Conjugates between methotrexate (MTX, Matrex, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-l-glutamic acid), an antifolate cancer chemotherapeutic to which resistance is often observed, and motexafin gadolinium (MGd), an experimental agent demonstrating selective tumor localization, are described. These systems were prepared in order to test whether linking these two species would produce agents with enhanced activity relative to MTX alone. Both ester- and amide-linked conjugates were synthesized starting from MGd and MTX.