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American Chemical Society, Journal of Medicinal Chemistry, 15(50), p. 3434-3441, 2007

DOI: 10.1021/jm061435l

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Platinum Complexes Can Inhibit Matrix Metalloproteinase Activity:  Platinum−Diethyl[(methylsulfinyl)methyl]phosphonate Complexes as Inhibitors of Matrix Metalloproteinases 2, 3, 9, and 12

Journal article published in 2007 by Rossella Sasanelli, Angelina Boccarelli ORCID, Domenico Giordano, Mariarita Laforgia, Fabio Arnesano, Giovanni Natile, Cosimo Cardellicchio, Maria A. M. Capozzi, Mauro Coluccia
This paper was not found in any repository; the policy of its publisher is unknown or unclear.
This paper was not found in any repository; the policy of its publisher is unknown or unclear.

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Abstract

Platinum complexes able to inhibit matrix metalloproteinases (MMPs) through a noncompetitive mechanism are reported for the first time in this study. [PtCl2(SMP)] and [Pt(dimethylmalonato)(SMP)], characterized by the bisphosphonate-analogue ligand diethyl[(methylsulfinyl)methyl]phosphonate (SMP), are slight inhibitors of MMP-2 (IC50 = 258 +/- 38 and 123 +/- 14 mu M, respectively) but markedly inhibit MMP-9 (IC50 = 35.5 +/- 6 and 17 +/- 4 mu M), MMP-3 (IC50 = 5.3 +/- 2.9 and 4.4 +/- 2.2 mu M), and MMP-12 (IC50 = 10.8 +/- 3 and 6.2 +/- 1.8 mu M). In contrast, cisplatin, carboplatin, and the SMP ligand are inactive, and the bisphosphonate clodronate shows a broad-spectrum inhibitory activity in the high micromolar range (mean IC50 > 200 mu M). These results, along with mechanistic investigations (DNA interaction and tumor cell growth inhibition), demonstrate that ligand modifications of platinum compounds can be exploited to target also biological substrates distinct from DNA.