Department of Pharmaceutical Chemistry, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria.
Dalton Trans. 2020 May 7;49(17):5471-5481. doi: 10.1039/c9dt04824c. Epub 2020 Apr 7.
Bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complexes (8a-h) with methoxy, methyl and fluorine substituents at different positions of the 4-aryl ring were synthesized and characterized. The relevance of the 2-methoxypyridin-5-yl residue and the substituents at the 4-aryl ring with regard to the activity against a series of cell lines was determined. Particularly against the Cisplatin-resistant ovarian cancer cell line A2780cis, the most active bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complex 8c was more active than Auranofin. It also inhibited thioredoxin reductase more effectively and induced high amounts of reactive oxygen species in A2780cis cells. Furthermore, its influence on non-cancerous SV 80 lung fibroblasts was lower than that of Auranofin. This fact, together with a high accumulation rate in tumor cells, determined on the example of MCF-7 cells, makes this complex an interesting candidate for further extensive studies.
合成并表征了具有甲氧基、甲基和氟取代基的溴代[3-乙基-4-芳基-5-(2-甲氧基吡啶-5-基)-1-丙基-1,3-二氢-2H-咪唑-2-亚基]金（I）配合物（8a-h），其中芳基环的不同位置具有取代基。确定了 2-甲氧基吡啶-5-基残基和 4-芳基环上取代基对一系列细胞系活性的相关性。特别是对顺铂耐药卵巢癌细胞系 A2780cis，最具活性的溴代[3-乙基-4-(4-甲氧基苯基)-5-(2-甲氧基吡啶-5-基)-1-丙基-1,3-二氢-2H-咪唑-2-亚基]金（I）配合物 8c 比 Auranofin 更具活性。它还能更有效地抑制硫氧还蛋白还原酶，并在 A2780cis 细胞中诱导大量活性氧。此外，它对非癌细胞 SV 80 肺成纤维细胞的影响低于 Auranofin。这一事实，以及在 MCF-7 细胞上确定的该复合物在肿瘤细胞中的高积累率，使其成为进一步广泛研究的有趣候选物。
