Several platinum (II) compounds are known to demonstrate anticancer activity. In particular, platinum complexes with a single chloride leaving ligand and three nitrogen containing ligands are known to contribute significantly to cell toxicity. Here, we have synthesized analogs of these complexes in which one ligand coordinates to the platinum atom through three distinct nitrogen atoms in a triamine complex.<br/><br/>Our platinum compound was reacted with an amino acid (N-acetyl-L-methionine, N-AcMet) and a nucleotide (guanosine monophosphate, 5'-GMP) with the expectation that either the methionine or the guanine would react. However, under some conditions, both the methionine and the guanine were shown to react with the platinum compound. At pH of 4 or higher, the methionine analog coordinated with the platinum drug via the sulfur atom, forming a final product that did not react with guanine. In separate reactions with N-AcMet and 5'-GMP, the former reacted faster than the latter. The reaction of methionine with the platinum drug at a lower pH produced an intermediate complex that could react with 5'-GMP to displace a portion of the triamine ligand.<br/><br/>The unique behavior of our compound is one that may be exploited in the design of future platinum-based drugs. An insight into the conditions that cause such unusual behavior could potentially be used to improve the efficacy of anticancer drugs used in chemotherapeutics.

Partial displacement of a triamine ligand from platinum (II) by guanosine 5'-monophosphate

251st National Meeting (2016)

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