Suppr超能文献

新型针对Huh7(肝癌)和Du145(前列腺癌)癌细胞系的定制RNA靶向有机金属候选药物。

New Tailored RNA-Targeted Organometallic Drug Candidates against Huh7 (Liver) and Du145 (Prostate) Cancer Cell Lines.

作者信息

Khan Huzaifa Yasir, Maurya Santosh K, Siddique Hifzur R, Yousuf Shariq, Arjmand Farukh

机构信息

Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.

Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.

出版信息

ACS Omega. 2020 Jun 19;5(25):15218-15228. doi: 10.1021/acsomega.0c01206. eCollection 2020 Jun 30.

Abstract

New organometallic drug candidates [PhSn(HL)], , and [Ru(η---cymene)(HL)Cl], , were designed and synthesized by in situ reaction of a Schiff base ligand (HL) and diphenyltin dichloride and [RuCl(-cymene)], respectively. The drug candidates and have been characterized by spectroscopic methods (Fourier-transform infrared spectroscopy, UV-vis, and H/C NMR), elemental analysis, and single X-ray crystallographic studies (in case of ). The ground-state geometry optimization of and was performed by density functional theory calculations. The interaction of and with tRNA was assessed by absorption spectroscopy, cyclic voltammetry, circular dichroism, and ethidium bromide displacement assay using fluorescence emission spectroscopy to determine their potential to act as antitumor agents. The cytotoxicity of and was screened against human liver carcinoma (Huh7), prostate cancer (Du145), and the normal prostate cell line (PNT 2). The results implicated a dose-dependent growth inhibition of the two cancer cells at concentrations (2.5-15 μM) of and with the treatment after 48 h. Interestingly, revealed good selective activity toward the liver cancer cell line (Huh7). Furthermore, both the drug candidates and were found to be nontoxic toward the PNT 2 normal cell line. These studies lay a paradigm for rational efficacious drug design for chemotherapeutic intervention in cancers using new tailored organometallic drug entities; organotin(IV) and organoruthenium(II) have been demonstrated to be viable for the safe administration and specific targeted drug uptake by the resistant cancerous cell lines at low intracellular concentrations.

摘要

新型有机金属候选药物[PhSn(HL)]、[Ru(η-对异丙基苯)(HL)Cl]分别通过席夫碱配体(HL)与二氯化二苯基锡以及[RuCl(对异丙基苯)]的原位反应设计合成。候选药物[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]已通过光谱方法(傅里叶变换红外光谱、紫外可见光谱和氢碳核磁共振)、元素分析以及单晶X射线晶体学研究(针对[Ru(η-对异丙基苯)(HL)Cl])进行了表征。[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]的基态几何结构优化通过密度泛函理论计算完成。利用吸收光谱、循环伏安法、圆二色光谱以及使用荧光发射光谱的溴化乙锭置换试验评估了[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]与转运核糖核酸(tRNA)的相互作用,以确定它们作为抗肿瘤药物的潜力。针对人肝癌细胞系(Huh7)、前列腺癌细胞系(Du145)和正常前列腺细胞系(PNT 2)筛选了[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]的细胞毒性。结果表明,在浓度为2.5至15 μM的[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]作用48小时后,两种癌细胞呈现出剂量依赖性生长抑制。有趣的是,[Ru(η-对异丙基苯)(HL)Cl]对肝癌细胞系(Huh7)显示出良好的选择性活性。此外,发现候选药物[PhSn(HL)]和[Ru(η-对异丙基苯)(HL)Cl]对PNT 2正常细胞系均无毒性。这些研究为使用新型定制有机金属药物实体进行癌症化疗干预的合理有效药物设计树立了范例;已证明有机锡(IV)和有机钌(II)在低细胞内浓度下可安全给药并被耐药癌细胞系特异性摄取,从而实现靶向给药。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验