Synthesis, spectroscopic investigation, and DFT study of N,N'-disubstituted ferrocene-based thiourea complexes as potent anticancer agents.
Synthesis, spectroscopic investigation, and DFT study of N,N'-disubstituted ferrocene-based thiourea complexes as potent anticancer agents.
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DOI：
10.1039/c7dt04090c
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发表时间：
2018-02
影响因子：
4
通讯作者：
Faiza Asghar;S. Fatima;S. Rana;A. Badshah;I. Butler;M. Tahir
中科院分区：
文献类型：
--
作者：
Faiza Asghar;S. Fatima;S. Rana;A. Badshah;I. Butler;M. Tahir
本文报道了九种新的二茂铁硫脲（A1-A9）的合成、表征（FT-IR、多核（1H和13 C）NMR、AAS、拉曼和元素分析）、DNA结合（循环伏安法、紫外-可见光谱）和体外生物筛选。此外，还测定了化合物A8的单晶X射线结构。二茂铁基N，N ′-二取代硫脲是通过使二茂铁基苯胺与新制备的异硫氰酸酯在N2气氛下在干燥丙酮中反应而得到的。通过循环伏安法和紫外-可见光谱法进行的DNA结合研究产生的结果对于结合常数（K）彼此非常一致，并且观察到静电相互作用模式。用密度泛函理论（DFT）/B3 LYP方法计算了优化结构的电荷分布和HOMO/LUMO能量。DFT计算的HOMO和LUMO能量与实验测定的氧化还原电位值相关良好。所合成的二茂铁基硫脲对1，1-二苯基-2-苦肼基自由基（DPPH）具有良好的清除活性。还扫描了这些复合物对MCF-7癌细胞以及对非癌细胞系MCF-10A的体外细胞毒性活性。结果显示，与标准化疗药物（顺铂）相比，对受试癌细胞系的细胞毒性适中。然而，这些二茂铁基衍生物在正常细胞中具有较少的毒性作用。
In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and 13C) NMR, AAS, Raman, and elemental analyses), DNA binding (cyclic voltammetry, UV-Vis spectroscopy), and in vitro biological screening of nine new ferrocene-incorporated thioureas (A1-A9) are reported. Furthermore, the single-crystal X-ray structure of compound A8 was also determined. The ferrocene-based N,N'-disubstituted thioureas were derived by allowing the ferrocenyl anilines to react with freshly prepared isothiocyanates under a N2 atmosphere in dry acetone. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl thioureas exhibited good scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxic activity against MCF-7 carcinoma cells, and also towards the non-cancerous cell line MCF-10A. The results showed modest cytotoxicity against the subjected cancer cell line compared with a standard chemotherapeutic drug (cisplatin). However, these ferrocenyl derivatives have fewer toxic effects in normal cells.