Testosterone as a delivery vector for platinum(II) metallodrugs

Abstract

A total of 6 steroidal ligands have been synthesised from simple starting materials using Sonogashira coupling reactions. The ligands are based on testosterone substituted in the l7a-position with ethnynyl-pyridine, ethnynyl-quinoline or ethnynyl-isoquinoline. A range of platinum(II) complexes have been synthesised using these ligands of the type trans- and cis- [Pt(NH3)2(L)(Cl][N03], where L is the steroidal ligand, alongside control complexes containing simple aromatic amines for comparison. The addition of the steroid imparted a substantional ability of the steroidal platinum(II) complexes to alter the structure of B-DNA. Furthermore, the steroid imparted cytotoxicity onto the complexes, which were very much more active that the steroidal ligand alone or platinum(II) complexes containing only an aromatic amine. Moreover, forcing the steroidal skeleton closer to DNA using 3-substituted pyridine rings and cis-geometries caused greater DNA unwinding, which is likely to relate to direct interactions between the DNA helix and the steroidal skeleton