Non-Medical Applications of Inorganic Medicines. A Switch Based on Mechanistic Knowledge.

Lorenzo Chiaverini, Iogann Tolbatov, Diego La Mendola, Damiano Cirri, Tiziano Marzo, Alessandro Marrone, Riccardo Di Leo, Alessandro Pratesi, Luigi Messori

Journal: Chemistry (Weinheim an der Bergstrasse, Germany) 2024;30(60):e202402647

PMID: 39158114

Abstract

Metals have been used in medicine for centuries. However, it was not until much later that the effects of inorganic drugs could be rationalized from a mechanistic point of view. Today, thanks to the technologies available, this approach has been functionally developed and implemented. It has been found that there is probably no single biological target for the pharmacological effects of most inorganic drugs. Herein, we present an overview of some integrated and multi-technique approaches to elucidate the molecular interactions underlying the biological effects of metallodrugs. On this premise, selected examples are used to illustrate how the information obtained on metal-based drugs and their respective mechanisms can become relevant for applications in fields other than medicine. For example, some well-known metallodrugs, which have been shown to bind specific amino acid residues of proteins, can be used to solve problems related to protein structure elucidation in crystallographic studies. Diruthenium tetraacetate can be used to catalyze the conversion of hydroxylamines to nitrones with a high selectivity when bound to lysozyme. Finally, a case study is presented in which an unprecedented palladium/arsenic-mediated catalytic cycle for nitrile hydration was discovered thanks to previous studies on the solution chemistry of the anticancer compound arsenoplatin-1 (AP-1).

© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.

Address: Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi, 13, 56124, Pisa, Italy.; Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy.; Department of Physics and Astronomy, University of Padova, Via F. Marzolo 8, 35131, Padova, Italy.; Department of Pharmacy, University "G. D'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100, Chieti, Italy.; Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.

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