Zhang Bo, Lu Xiaoming, Wang Guo, Zhang Weichuan, Xia Sifeng, Chen Yuyou
Department of Chemistry, Capital Normal University, Beijing 100048, China.
Department of Chemistry, Capital Normal University, Beijing 100048, China; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
J Inorg Biochem. 2014 Nov;140:213-8. doi: 10.1016/j.jinorgbio.2014.07.023. Epub 2014 Aug 7.
In order to seek better ligand for anticancer drug, we choose 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) as predominant ligands, and synthetize two complexes:[(DMF)Cu(phen)(NO3)2] (1) and [(DMF)Cu(2,9-dmp)(NO3)2] (2) (DMF is dimethyl formamide). As for the five kinds of cancer cells, including A-549, Bel-7402, HCT-8, MDCK and L-1210 cells, our complexes showed higher inhibition ratio compared with anticancer drug 5-Fu (fluorouracil), ligand phenanthroline and Cu(NO3)2. It's worth noting that complex 2's anticancer activity is much more efficient than that of complex 1. This is because there are di-substituted-methyl in 2,9-dmp. By calculating, we found Δcomplexes<Δphenanthroline which showed that the energy gap between π(⁎) and π of the phenanthroline is decreased through coordination with Cu(II). Computational ΔG2<ΔG, and bond length (CuN)1<(CuN)2 revealed that the coordinated 2,9-dmp is easier to dissociate with Cu(II) than phen, which is confirmed by the absorption peak at 460nm in UV-visible (UV-vis) spectra of complex 2. In summary, the phenanthroline is activated by Cu(II)-coordination, which is beneficial for anticancer. More importantly, the substituted-methyl radicals stimulated the phenanthroline and enhanced the anticancer properties more efficiently.
为了寻找更好的抗癌药物配体，我们选择1,10-菲咯啉（phen）和2,9-二甲基-1,10-菲咯啉（2,9-dmp）作为主要配体，并合成了两种配合物：[(DMF)Cu(phen)(NO3)2] (1) 和 [(DMF)Cu(2,9-dmp)(NO3)2] (2)（DMF为二甲基甲酰胺）。对于包括A-549、Bel-7402、HCT-8、MDCK和L-1210细胞在内的五种癌细胞，我们的配合物与抗癌药物5-氟尿嘧啶（5-Fu）、配体菲咯啉和Cu(NO3)2相比，显示出更高的抑制率。值得注意的是，配合物2的抗癌活性比配合物1高得多。这是因为2,9-dmp中有二取代甲基。通过计算，我们发现Δ配合物<Δ菲咯啉，这表明菲咯啉的π(⁎)和π之间的能隙通过与Cu(II)配位而减小。计算得到ΔG2<ΔG，且键长(CuN)1<(CuN)2，这表明配位的2,9-dmp比phen更容易与Cu(II)解离，这在配合物2的紫外可见（UV-vis）光谱中460nm处的吸收峰得到证实。综上所述，菲咯啉通过与Cu(II)配位而被激活，这有利于抗癌。更重要的是，取代甲基自由基刺激了菲咯啉并更有效地增强了抗癌性能。
