Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada.
Curr Top Med Chem. 2012;12(3):122-44. doi: 10.2174/156802612799078973.
This review will highlight recent advances in ligand design for innovative applications in medicinal inorganic chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. In an effort to achieve this goal, compounds are being developed that either target a disease site, or are activated by a disease specific biological process. Metal complexes containing targeting functions and/or bioactive ligands, as well as agents that are activated by specific enzymes, or changes in pH and pO2, provide new avenues for drug development. Radiodiagnostic compounds, magnetic resonance imaging agents, and optical probes containing transition metals offer versatility unavailable to organic imaging agents. In certain cases, dual modality agents have been developed, and will be highlighted. Finally, we will discuss targeted metal binding compounds for treatment of metal overload disorders, and the recent application to neurodegenerative disease.
这篇综述将重点介绍配体设计方面的最新进展，这些进展将为医学无机化学的创新应用带来新的契机。配体能够有效地与金属离子结合，同时还包含特定的特征，以增强靶向性、报告功能和整体疗效，从而推动了疾病诊断和治疗领域的创新。提高治疗化合物的效力，同时限制副作用，是医学化学中的一个常见目标。为了实现这一目标，人们正在开发针对疾病部位的化合物，或者通过特定的生物过程来激活化合物。含有靶向功能和/或生物活性配体的金属配合物，以及受特定酶、pH 值和 pO2 变化激活的试剂，为药物开发提供了新的途径。含有过渡金属的放射性诊断化合物、磁共振成像剂和光学探针提供了有机成像剂所不具备的多功能性。在某些情况下，已经开发出了双模态试剂，并将对其进行重点介绍。最后，我们将讨论用于治疗金属过载疾病的靶向金属结合化合物，以及最近在神经退行性疾病中的应用。
