School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Organic Chemistry Laboratory, University of Bayreuth, Universitätsstr. 30, 95440 Bayreuth, Germany.
Molecules. 2018 Aug 14;23(8):2031. doi: 10.3390/molecules23082031.
Ten novel -heterocyclic carbene gold(I) complexes derived from lepidiline A (1,3-dibenzyl-4,5-dimethylimidazolium chloride) are reported here with full characterisation and biological testing. (1,3-Dibenzyl-4,5-diphenylimidazol-2-ylidene)gold(I) chloride (NHC*-AuCl) () was modified by substituting the chloride for the following: cyanide (), dithiocarbamates (⁻), -mercaptobenzoate derivatives (⁻) and -acetyl-l-cysteine derivatives (⁻). All complexes were synthesised in good yields of 57⁻78%. Complexes , , , and were further characterised by X-ray crystallography. Initial evaluation of the biological activity was conducted on all ten complexes against the multidrug resistant MCF-7 breast cancer, HCT-116, and p53 knockout mutant HCT-116 colon carcinoma cell lines. Across the three cell lines tested, mainly single-digit micromolar IC values were observed. Nanomolar activity was exhibited on the MCF-7 cell line with displaying an IC of 0.28 μM ± 0.03 μM. Complexes incorporating a Au⁻S bond resulted in higher cytotoxic activity when compared to complexes and . Theoretical calculations, carried out at the MN15/6⁻311++G(2df,p) computational level, show that NHC* is the more favourable ligand for Au(I)-Cl when compared to PPh₃.
报告了十种新型杂环卡宾金（I）配合物，这些配合物衍生自利培啶 A（1,3-二苄基-4,5-二甲基咪唑𬭩氯化物），并对其进行了全面的表征和生物学测试。（1,3-二苄基-4,5-二苯基咪唑-2-亚基）金（I）氯化物（NHC*-AuCl）（）被修饰，用以下物质取代了氯化物：氰化物（）、二硫代氨基甲酸盐（-）、-巯基苯甲酸酯衍生物（-）和 -乙酰基-l-半胱氨酸衍生物（-）。所有配合物均以 57-78%的良好产率合成。配合物 、 、 、和 进一步通过 X 射线晶体学进行了表征。对所有十种配合物针对多药耐药 MCF-7 乳腺癌、HCT-116 和 p53 缺失突变 HCT-116 结肠癌细胞系的生物活性进行了初步评估。在所测试的三种细胞系中，主要观察到十位数微摩尔 IC 值。在 MCF-7 细胞系中表现出纳米摩尔活性，其中 显示出 0.28 μM ± 0.03 μM 的 IC 值。与配合物 和 相比，含有 Au-S 键的配合物表现出更高的细胞毒性活性。在 MN15/6-311++G(2df,p)计算水平上进行的理论计算表明，与 PPh₃ 相比，NHC* 是 Au(I)-Cl 的更有利配体。
