REQUIMTE-CQFB, Departamento de Química, FCT-UNL, 2829-516 Caparica, Portugal.
Curr Med Chem. 2011;18(22):3361-6. doi: 10.2174/092986711796504583.
The biological role of carbon monoxide (CO) has completely changed in the last decade. Beyond its widely feared toxicity, CO has revealed a very important biological activity as a signaling molecule with marked protective actions namely against inflammation, apoptosis and endothelial oxidative damage. Its direct use as a therapeutic gas showed significant and consistent positive results but also intrinsic severe limitations. The possibility of replacing the gas by pro-drugs acting as CO-Releasing Molecules (CO-RMs) has clearly been demonstrated with several experimental compounds. Transition metal carbonyls complexes have proven to be the most versatile experimental CO-RMs so far. Presently, the challenge is to equip them with drug-like properties to turn them into useful pharmaceuticals. This requires studying their interactions with biological molecules namely those that control their pharmacokinetic and ADME profiles like the plasma proteins. In this account we analyze these questions and review the existing interactions between Metal Carbonyls and proteins. The recently explored case of CORM-3 is revisited to exemplify the methodologies involved and the importance of the results for the understanding of the mode of action of such pro-drugs.
在过去的十年中，一氧化碳（CO）的生物学作用发生了彻底的变化。除了广为人知的毒性之外，CO 还显示出一种非常重要的生物活性，作为一种信号分子，具有显著的保护作用，特别是针对炎症、细胞凋亡和内皮氧化损伤。其直接作为治疗气体的应用显示出了显著而一致的积极结果，但也存在内在的严重局限性。用几种实验化合物已经清楚地证明了用前药作为一氧化碳释放分子（CO-RMs）来替代气体的可能性。过渡金属羰基配合物已被证明是迄今为止最通用的实验 CO-RMs。目前，面临的挑战是赋予它们类药物特性，将它们转化为有用的药物。这需要研究它们与生物分子的相互作用，特别是那些控制其药代动力学和 ADME 特征的生物分子，如血浆蛋白。在本报告中，我们分析了这些问题，并回顾了金属羰基化合物与蛋白质之间的现有相互作用。重新考察了最近探索的 CORM-3 案例，以举例说明所涉及的方法学以及这些结果对于理解此类前药作用模式的重要性。
