Ansari Eklakh, Kumar Ravi, Ratnam Anand
Department of Chemistry, DDU Gorakhpur University, Gorakhpur-273009, India.
Department of Chemistry, National Institute of Technology, Srinagar, 190006, India.
Dalton Trans. 2025 May 13;54(19):7553-7601. doi: 10.1039/d5dt00118h.
Recent advancements in Au(I)-N-heterocyclic carbene (NHC) complexes have demonstrated significant potential for developing novel anticancer agents. These complexes exhibit unique properties, such as a strong affinity for thiol and selenol-containing biomolecules, which enable the selective targeting of cancer cells while minimising effects on healthy tissues. Recent studies have explored various structural modifications to enhance the anticancer efficacy of Au(I)-NHC complexes, including ligand substitution, incorporation of bioactive moieties, and hybridisation with other metal complexes. Mechanistic investigations have revealed that these complexes induce apoptosis through multiple pathways, such as inhibition of thioredoxin reductase (TrxR), disruption of mitochondrial function, and generation of reactive oxygen species (ROS). The introduction of NHC ligands is particularly advantageous, as they provide stability and tunability to the Au(I) centre, allowing for the optimisation of pharmacokinetic and pharmacodynamic properties. Moreover, the emergence of Au(I)-NHC complexes with dual-action mechanisms, combining anticancer activity with antiangiogenic or anti-inflammatory properties, has further broadened their therapeutic potential. This review article highlights the most recent breakthroughs in the design, synthesis, and biological evaluation of Au(I)-NHC complexes, emphasizing their promise as a new class of targeted anticancer therapeutics. While primarily focused on Au(I) complexes, it also includes a brief discussion of selected Au(III) complexes for comparison.
金(I)-N-杂环卡宾(NHC)配合物的最新进展已显示出开发新型抗癌药物的巨大潜力。这些配合物具有独特的性质,例如对含硫醇和含硒醇的生物分子具有很强的亲和力,这使得它们能够选择性地靶向癌细胞,同时将对健康组织的影响降至最低。最近的研究探索了各种结构修饰,以提高金(I)-NHC配合物的抗癌疗效,包括配体取代、引入生物活性部分以及与其他金属配合物杂交。机理研究表明,这些配合物通过多种途径诱导细胞凋亡,如抑制硫氧还蛋白还原酶(TrxR)、破坏线粒体功能以及产生活性氧(ROS)。引入NHC配体特别有利,因为它们为金(I)中心提供了稳定性和可调节性,从而可以优化药代动力学和药效学性质。此外,具有双重作用机制的金(I)-NHC配合物的出现,将抗癌活性与抗血管生成或抗炎特性相结合,进一步拓宽了它们的治疗潜力。这篇综述文章重点介绍了金(I)-NHC配合物在设计、合成和生物学评价方面的最新突破,强调了它们作为一类新型靶向抗癌治疗药物的前景。虽然主要关注金(I)配合物,但也包括对选定的金(III)配合物进行比较的简要讨论。