Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
J Inorg Biochem. 2012 Apr;109:97-106. doi: 10.1016/j.jinorgbio.2011.12.007. Epub 2011 Dec 29.
The peculiar chemical properties of metal-based drugs impart innovative pharmacological profiles to this class of therapeutic and diagnostic agents, most likely in relation to novel molecular mechanisms still poorly understood. However, inorganic drugs have been scarcely considered for medicinal applications with respect to classical organic compounds due to the prejudice of the relevant toxic effects evidenced in certain cases. Thus, the development of improved metallodrugs requires clearer understanding of their physiological processing and molecular basis of actions. Among the various issues in the area of medicinal inorganic chemistry, the possibility of target elucidation is essential for the identification of new therapeutic applications for metal compounds or as molecular biological tools. Here we present the results of our recent research in the field, which in our opinion constitute the basis of a systematic and interdisciplinary approach to address some of the critical issues in the study of the molecular mechanisms of metallodrugs' action via the implementation of high-resolution biophysical techniques coupled with more pharmacological methods.
金属药物的特殊化学性质赋予了这类治疗和诊断药物创新的药理学特性,这很可能与尚未完全理解的新型分子机制有关。然而,由于在某些情况下发现了相关的毒性作用,无机药物在医学应用方面几乎没有被考虑用于经典有机化合物。因此,为了开发改良的金属药物,需要更清楚地了解它们的生理处理和作用的分子基础。在医学无机化学领域的各种问题中,阐明靶标的可能性对于确定金属化合物的新治疗应用或作为分子生物学工具是至关重要的。在这里,我们展示了我们在该领域的最新研究结果,我们认为这些结果是通过实施高分辨率生物物理技术并结合更多药理学方法来解决金属药物作用的分子机制研究中的一些关键问题的系统和跨学科方法的基础。