Substitution-Inert Trinuclear Platinum Complexes Efficiently Condense/Aggregate Nucleic Acids and Inhibit Enzymatic Activity

Published: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 53, 12812-12816 Authors: Malina, J., Farrell, NP., Brabec, V. Year: 2014

Abstract

The trinuclear platinum complexes (Triplatin NC-A [{Pt(NH3)(3)}(2)-mu-{trans-Pt(NH3)(2)(NH2(CH2)(6)NH2)(2)}](6+), and Triplatin NC [{trans-Pt(NH3)(2)(NH2(CH2)(6)NH3+)}(2)-mu-{trans-Pt(NH3)(2)(NH2(CH2)(6)NH2)(2)}](8+)) are biologically active agents that bind to DNA through noncovalent (hydrogen bonding, electrostatic) interactions. Herein, we show that TriplatinNC condenses DNAwith a much higher potency than conventional DNA condensing agents. Both complexes induce aggregation of small transfer RNA molecules, and TriplatinNC in particular completely inhibits DNA transcription at lower concentrations than naturally occurring spermine. Topoisomerase Imediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at concentrations which were 60 times and 250 times lower than that of spermine. The mechanisms for the biological activity of TriplatinNC-A and TriplatinNC may be associated with their ability to condense/aggregate nucleic acids with consequent inhibitory effects on crucial enzymatic activities.