Farooq Muhammad, Taha Nael Abu, Butorac Rachel R, Evans Daniel Anthony, Elzatahry Ahmed A, Elsayed Elsayed Ahmed, Wadaan Mohammad A M, Al-Deyab Salem S, Cowley Alan H
Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Chemistry, the University of Texas at Austin, Austin, TX 78712, USA.
Int J Mol Sci. 2015 Oct 16;16(10):24718-31. doi: 10.3390/ijms161024718.
N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10-12 h. One hundred percent mortality was observed at concentrations≥50 µM. At sub-lethal concentrations (10-30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%-40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.
N-杂环卡宾（NHC）金属配合物具有多种生物活性，但作为潜在的化疗药物尚未得到广泛研究。我们之前报道了一类新型的带有乙酸盐[IPr(BIAN)AuOAc]和氯化物[IPr(BIAN)AuCl]配体的N-杂环NHC金属配合物的合成。在本文报道的实验中，斑马鱼胚胎暴露于这些配合物的系列稀释液中10 - 12小时。在浓度≥50 µM时观察到100%的死亡率。在亚致死浓度（10 - 30 µM）下，这两种化合物都影响了斑马鱼胚胎的发育。然而，在每种化合物处理的胚胎中发现了相当不同类型的异常。在[IPr(BIAN)AuOAc]处理的情况下，明显出现严重的脑变形和脊索退化。用[IPr(BIAN)AuCl]处理的斑马鱼胚胎生长发育迟缓，因此体型较小。在处理过的胚胎中检测到谷胱甘肽消耗了30% - 40%，这可能是神经毒性的一种可能机制。这些化合物既能影响生长又能通过提高细胞内活性氧的产生来损害抗氧化系统，这一事实意味着它们作为一类新型治疗分子可能发挥重要作用。
