Abstract
trans-Platinum complexes have been the landmark in unconventional drugs prompting the development of innovative structures that might exhibit chemical and biological profiles different to cisplatin. Iodido complexes signaled a new turning point in the platinum drug design field when their cytotoxicity was reevaluated and reported. In this new study, we have synthesized and evaluated diodidoplatinum complexes trans-[PtI2(amine)(pyridine)] bearing aliphatic amines (isopropylamine and methylamine) and pyridines in trans configuration. X-ray diffraction data support the structural characterization. Their cytotoxicity has been evaluated in tumor cell lines such as SAOS-2, A375, T-47D, and HCT116. Moreover, we report their solution behavior and reactivity with biological models. Ultraviolet-a (UVA) irradiation induces an increase in their reactivity towards model nucleobase 5′-GMP in early stages, and promotes the release of the pyridine ligand (spectator ligand) at longer reaction times. Density Functional calculations have been performed and the results are compared with our previous studies with other iodido derivatives.
Highlights
IntroductionThe latest reviews and the large number of contributions therein identify new complex designs to face the known side effect problems of these antitumor drugs [1]
Antitumor platinum drug design has been and still is a major project in metallodrug research.The latest reviews and the large number of contributions therein identify new complex designs to face the known side effect problems of these antitumor drugs [1]
(amine)(pyridine)] complexes complexes were were prepared prepared according according to published procedures
Summary
The latest reviews and the large number of contributions therein identify new complex designs to face the known side effect problems of these antitumor drugs [1]. Looking for a new design, our group of researchers reevaluated cis platinum iodido complexes; their reactivity turned out to be quite unexpected versus sulfur donor biomolecules [4]. Our studies proved that the iodido groups stayed in the adducts formed in the reaction with the protein cytochrome c or lysozime while the aliphatic amines acted as leaving groups [5]. This peculiar reactivity was not detected versus DNA, with which they showed classical reactivity cisplatin like
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