PdII and PtII complexes with a thio-aza macrocycle ligand containing an intercalating fragment: Structural and antitumor activity studies

Abstract

Two new Pt^II and Pd^II complexes of formula [LMCl₂] (M=Pt, Pd) were synthesized and characterized both in solution and solid state. They were obtained using the thio-aza macrocycle 9,18-dimethyl-12,17dithia-9,18,27,28-tetraaaza-29-oxatetracyclo[24.2.1.0^2,7.0^20,25]enneicosa-2,4,6,20,22,24,26,28¹-octaene (L) containing the 2,5-diphenyl [1, 3, 4]oxadiazole as intercalating fragment. M^II is coordinated in cis-position by the two S atoms of L. The two crystal structures of [LPtCl₂] and [LPdCl₂] complexes showed that the M^II ion is located outside the macrocyclic cavity. The square planar coordination sphere is fulfilled by two chloride anions in a cisplatin-like arrangement with the chloride leaving groups exposed to the environment. The biological activity of both [LPtCl₂] and [LPdCl₂], monitored towards a leukemic cellular model (U937), is coherent with their ability to interfere, at different levels, with the DNA structure.

Keywords: Antineoplastic drugs; Cancer; Macrocycle; Palladium complexes; Platinum complexes.