Xu Zhi Dong, Liu He, Wang Min, Xiao Su Long, Yang Ming, Bu Xian He
National Research Laboratory of Natural and Biomimetic Drugs, Peking University, 100083, Beijing, PR China.
J Inorg Biochem. 2002 Nov 25;92(3-4):149-55. doi: 10.1016/s0162-0134(02)00569-x.
A new Mn(II) complex with the planar ligand 6,7-dicycanodipyrido[2,2-D:2',3'-f]quinoxaline (L) [MnL(NO(3))(H(2)O)(3)]NO(3).CH(3)OH (1) has been synthesized and characterized by elemental analysis, IR, TG-DTA and molar conductance. Its crystal structure was determined by X-ray diffraction, crystal data: yellow, triclinic, space group P1;, Z=2, a=7.3743(8) A, b=11.2487(15) A, c=14.1655(15) A, alpha=79.412(2) degrees, beta=83.208(2) degrees, gamma=80.466(2) degrees. The Mn atom was hexa-coordinated to form a distorted octahedral geometry by two nitrogen atoms of L and four oxygen atoms of three H(2)O and NO(3)(-) in the complex. The binding mode of the complex with calf thymus DNA has also been investigated with spectrophotometric methods, viscosity and thermal denaturation measurements. The experimental results indicate that the complex intercalated into DNA base pairs via the ligand L. The intrinsic binding constant K(b) values for 1 (5.00 x 10(5) M(-1)) and L (1.65 x 10(5) M(-1)) were determined by absorption titration and calculated with the model of McGhee and Von Hippel. Biological tests against four different cell lines (HL-60, KB, Hela and BGC-823) in vitro showed that the complex had significant antitumor properties since the 50% inhibition concentrations (IC(50)) of the complex were within a microM range similar to those of antitumor drug 5-fluorouracil.
合成了一种新的锰（II）配合物[MnL(NO(3))(H(2)O)(3)]NO(3).CH(3)OH（1），其中配体为平面型的6,7-二氰基二吡啶并[2,2-D:2',3'-f]喹喔啉（L），并通过元素分析、红外光谱、热重-差示热分析和摩尔电导率对其进行了表征。通过X射线衍射确定了其晶体结构，晶体数据如下：黄色，三斜晶系，空间群P1；Z = 2，a = 7.3743(8) Å，b = 11.2487(15) Å，c = 14.1655(15) Å，α = 79.412(2)°，β = 83.208(2)°，γ = 80.466(2)°。在该配合物中，锰原子通过配体L的两个氮原子以及三个H(2)O和NO(3)(-)的四个氧原子进行六配位，形成扭曲的八面体几何构型。还采用分光光度法、粘度和热变性测量等方法研究了该配合物与小牛胸腺DNA的结合模式。实验结果表明，该配合物通过配体L插入到DNA碱基对中。通过吸收滴定法测定了配合物1（5.00×10(5) M(-1)）和配体L（1.65×10(5) M(-1)）的固有结合常数K(b)值，并根据McGhee和Von Hippel模型进行计算。体外针对四种不同细胞系（HL-60、KB、Hela和BGC-823）的生物学测试表明，该配合物具有显著的抗肿瘤特性，因为其50%抑制浓度（IC(50)）处于与抗肿瘤药物5-氟尿嘧啶相似的微摩尔范围内。
