Synthesis and biological evaluation of platinum-acridine hybrid agents modified with bipyridine non-leaving groups

铂-吖啶杂化试剂的合成及生物学评价,该杂化试剂经联吡啶非离去基团修饰

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Abstract

The use of 2,2'-bipyridines (4,4'-R(2)-2,2'-bpy; R=H, Me, OMe, CF(3)) as non-leaving groups (L-L) in platinum-acridinylthiourea conjugates, [PtCl(L-L)(ACRAMTU)](NO(3))(2), has been investigated. All bpy-substituted complexes (2-5) show micromolar activity in HL-60 (leukemia) and H460 (lung) cancer cell lines but proved to be significantly less potent than the prototypical compound (1) containing aliphatic ethane-1,2-diamine. NMR and mass spectrometry data indicate that bpy accelerates the reaction of platinum with DNA nitrogen, but the resulting adducts are more labile than those formed by the prototype.

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