Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi, 13, 56124 Pisa, Italy.
Departamento de Química, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain.
J Inorg Biochem. 2020 Apr;205:110998. doi: 10.1016/j.jinorgbio.2020.110998. Epub 2020 Jan 15.
A silver(I) and a gold(I) complex of the fluorescent N-heterocyclic carbenic (NHC) ligand 1-(9-anthracenylmethyl)-3-(3-trimethylsilyl-2-propynil)-benzimidazol-2-ylidene have been synthesized and characterized. These compounds show cytotoxicity in the micromolar range and higher antiproliferative properties than cisplatin (CDDP) against several tumour cell lines such as SW480 (colon), A549 (lung) and HepG2 (liver). Both metal complexes are successfully internalized by SW480 cells being the silver compound the most accumulated. Subsequently, they were evaluated as inhibitors of the selenoenzyme Thioredoxin reductase (TrxR) and as DNA binders. Fluorescence microscopy confirmed that both protein and DNA binding could be involved in the biological activity of the compounds. The silver carbene was the most effective enzyme inhibitor with an IC in the nanomolar range. Also, interaction studies with natural double stranded DNA highlight a strong stabilisation of the double helix after binding to the Ag(I) carbene, indicating its potential suitability as dual-targeting anticancer active molecule.
已经合成并表征了荧光 N-杂环卡宾（NHC）配体 1-（9-蒽甲基）-3-（3-三甲基硅基-2-丙炔基）苯并咪唑-2-亚基的银（I）和金（I）配合物。这些化合物在微摩尔范围内表现出细胞毒性，并且对几种肿瘤细胞系（如 SW480（结肠）、A549（肺）和 HepG2（肝））的增殖抑制作用高于顺铂（CDDP）。两种金属配合物都被 SW480 细胞成功内化，其中银配合物的积累最多。随后，它们被评估为硒酶硫氧还蛋白还原酶（TrxR）抑制剂和 DNA 结合剂。荧光显微镜证实，蛋白质和 DNA 结合都可能参与化合物的生物学活性。银卡宾是最有效的酶抑制剂，IC 在纳摩尔范围内。此外，与天然双链 DNA 的相互作用研究突出了与 Ag（I）卡宾结合后双链的强烈稳定化，表明其作为双靶向抗癌活性分子具有潜在的适用性。
