Esarev Igor V, Wu Chengnan, Kirsanova Anna A, Türck Sebastian, Lippmann Petra, Jones Peter G, Babak Maria V, Ott Ingo
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstraße 55, 38106, Braunschweig, Germany.
Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR, 999077, China.
Chem Asian J. 2025 Apr 3;20(7):e202401672. doi: 10.1002/asia.202401672. Epub 2025 Feb 6.
Silver N-heterocyclic carbene (NHC) complexes are known to form biscarbene species from monocarbene analogs in protic polar solvents. However, the effect of the respective species of silver NHC complexes on their biological activity against bacteria or cancer cells has not been systematically explored, either in vitro or in vivo. The direct and simple conversion of monocarbene silver N-heterocyclic carbene (NHC) halide complexes (NHC)AgX, (X=Cl, Br) 1 a/b-5 a/b to their biscarbene analogues (NHC)AgX 1 c/d-5 c/d is reported. The biscarbenes demonstrated generally lower activity against bacteria compared to the monocarbene complexes; however, both types showed similar activity against tumor cells and a non-tumor reference cell line. Selected mono- and biscarbene complexes 3 a and 3 c showed similar strong inhibitory effects on thioredoxin reductase in vitro and in cellulo and had a similar level of metal uptake into A549 cells. The subsequent evaluation of their effects in vivo revealed relatively low toxicity and high antitumoral efficacy of both selected complexes in mice. The biscarbene silver organometallic 3 c showed the most pronounced reduction of tumor growth in animals. The results indicate that both (NHC)AgX and (NHC)AgX complexes could trigger their anticancer activity as biscarbene complexes, making this the preferred form for future anticancer metallodrug development.
已知银氮杂环卡宾（NHC）配合物在质子性极性溶剂中能从单卡宾类似物形成双卡宾物种。然而，无论是在体外还是体内，银NHC配合物的各自物种对其抗细菌或癌细胞的生物活性的影响尚未得到系统研究。本文报道了单卡宾银氮杂环卡宾（NHC）卤化物配合物（NHC）AgX（X = Cl、Br）1 a/b - 5 a/b向其双卡宾类似物（NHC）AgX 1 c/d - 5 c/d的直接且简单的转化。与单卡宾配合物相比，双卡宾对细菌的活性通常较低；然而，这两种类型对肿瘤细胞和非肿瘤参考细胞系表现出相似的活性。选定的单卡宾和双卡宾配合物3 a和3 c在体外和细胞内对硫氧还蛋白还原酶显示出相似的强抑制作用，并且对A549细胞的金属摄取水平相似。随后对它们在体内作用的评估显示，所选两种配合物在小鼠中具有相对较低的毒性和较高的抗肿瘤功效。双卡宾银有机金属配合物3 c在动物中显示出最显著的肿瘤生长抑制作用。结果表明，（NHC）AgX和（NHC）AgX配合物都可以作为双卡宾配合物触发其抗癌活性，使其成为未来抗癌金属药物开发的首选形式。
