Galassi Rossana, Sargentoni Nicola, Renzi Sofia, Luciani Lorenzo, Bartolacci Caterina, Pattabhi Prasad, Andreani Cristina, Pucciarelli Stefania
Chemistry Division, School of Science and Technology, University of Camerino, ChIP Via Madonna delle Carceri, 62032 Camerino, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy.
Pharmaceuticals (Basel). 2024 Aug 28;17(9):1133. doi: 10.3390/ph17091133.
Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh were found to be more cytotoxic than homoleptic [(NHC)-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh (compound ) or the trigonal NHC-Au(Cl)PPh (compound ) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC ranging between 10-21 µM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound .
肺癌是全球癌症相关死亡的主要原因，需要更新疗法以对抗严重的副作用和耐药性的发生。本文采用一组非小细胞肺癌（NSCLC）细胞作为癌症模型。研究了八种结构相关的带有NHC和卤化物或三苯基膦配体的金（I）和金（III）配合物作为肺癌细胞生长抑制剂。正如预期的那样，发现含PPh的金化合物比纯配体[(NHC)-Au(I)]X或杂配体NHC-Au(I)X或NHC-Au(III)X配合物具有更高的细胞毒性。发现在中心金属处呈现线性NHC-AuPPh（化合物 ）或三角NHC-Au(Cl)PPh（化合物 ）排列的混合配体金（I）化合物是最佳的肺癌细胞毒性化合物。对处理过的细胞的TrxR残余活性分析表明，这些化合物有效地抑制了金化合物最认可的分子靶点TrxR，化合物 在肺癌细胞中的活性降低超过80%。目前一些肺癌治疗方案由特定的肺癌细胞细胞毒性剂与抗叶酸药物联合组成；有趣的是，本文中的金化合物既是TrxR抑制剂又是抗叶酸抑制剂。人DHFR受到抑制，IC值在10 - 21 μM之间，这取决于底物浓度，仅化合物 可能通过变构机制起作用。
