DNA-BINDING POLYAMIDE DRUG CONJUGATES

摘要

A conjugate of formula: V-(Y)a-Z-T: (I), T-X-B-(Y)a-Z-T': (II), V-(Y)a Z-(Y')a V': (III), T-X-B-(Y)a-Z-(Y')a-X'-B'-T': (IV), V-(Y)a-Z-(Y')a-X-B-T : (V), V-(Y)a-Z-X-B-Z'-(Y')a-(V')b: (VI), or (W)a-(Y)b-[(Z)c-(Y')d-(X-B)e-(Y")f-(Z')g]h-(Y ...)i-(W')j: (VII), in which W and W' are independently a DNA intercalator or terminal subunit, V and V' are independently a DNA intercalator, X and X' are independently a DNA alkylator, B and B' are the same or different and each is a heteroaromatic residue that is attached to the N­terminus of an alkylator subunit (X or X'), Y, Y', Y" and Y"' are independently a linker, T and T' are independently terminal subunits, Z and Z' are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of a conjugate of any of formulae (I)-(VII) or a composition comprising same.