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Abstract：
Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD50 of the complex at 500 mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400 mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200 mg/kg group. In the histopathological analysis, the 50, 100, and 200 mg/kg groups were not associated with any toxicological alterations, whereas the 400 mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200 mg/kg without any toxicological and genotoxic potential.
摘要：
在过去的几十年中，类黄酮被认为是一种强大的生物活性分子。这些类黄酮与金属离子的络合证明了独特的有机金属络合物的产生，该络合物提供了改善的药理和治疗活性。在这项研究中,合成了非塞素钌-对-异丙基苯并丙炔配合物，并通过不同的分析方法进行了表征，如紫外-可见光谱，傅里叶变换红外光谱,质谱,和扫描电子显微镜。通过急性和亚急性毒性评估了复合物的毒理学特征。此外,通过Ames试验评估复合物的诱变和基因毒性活性，染色体畸变试验,和瑞士白化病小鼠的微核分析。急性口服毒性研究显示复合物的LD50为500mg/kg，随后，选择亚急性剂量.在亚急性毒性研究中，400mg/kg组的血液学和血清生化显示白细胞上调，天冬氨酸转氨酶,丙氨酸氨基转移酶，碱性磷酸酶,肌酐,葡萄糖和胆固醇。然而,50,100和200mg/kg组的血液学和血清生化指标无治疗相关改变。在组织病理学分析中，50、100和200mg/kg组没有任何毒理学改变，而400mg/kg组表现出突出的毒理学发生率。然而，在瑞士白化病小鼠中，使用非塞素钌-对甲基丙炔复合物的治疗没有任何诱变和遗传毒性作用。因此，这种新型有机金属配合物的安全剂量被确定为50,100和200mg/kg，没有任何毒理学和基因毒性潜力。
