记者从华南农业大学获悉，该校理学院日前设计、合成了两个具有抗肿瘤活性的新型化合物。相关成果近日在线发表于英国皇家化学会期刊《道尔顿无机化学》。

据了解，关于金属配合物型抗肿瘤化合物的抗肿瘤活性及其作用机理方面的研究已经成为当今抗肿瘤药物研究开发的重要方向。其中，靶向DNA小沟特异碱基系列的金属配合物作为抗肿瘤试剂的研究备受关注。

以华南农业大学理学院应用化学专业硕士生傅夏兵为第一作者、乐学义教授为通讯作者的研究论文《作为潜在化疗药物的水溶性DNA小沟结合剂：制备、表征、DNA结合和断裂、抗氧化、抗肿瘤活性及与人血清白蛋白的作用》，以二肽、杂环化合物及生命元素铜为原料，设计、合成了两个具有抗肿瘤活性的新型化合物。

据介绍，这些化合物与目前得到广泛应用的抗肿瘤药物5—氟尿嘧啶相比，具有更好的抗肿瘤活性和更优良的溶解性。（来源：中国科学报 朱汉斌 方玮）

Water-soluble DNA minor groove binders as potential chemotherapeutic agents: synthesis, characterization, DNA binding and cleavage, antioxidation, cytotoxicity and HSA interactions

Abstract Two new water-soluble copper(II)-dipeptide complexes: [Cu(glygly)(PyTA)]ClO₄·1.5H₂O (1) and [Cu(glygly)(PzTA)]ClO₄·1.5H₂O (2) (glygly = glycylglycine anion, PyTA = 2,4-diamino-6-(2′-pyridyl)-1,3,5-triazine and PzTA = 2,4-diamino-6-(2′-pyrazino)-1,3,5-triazine), utilizing two interrelated DNA base-like ligands (PyTA and PzTA), have been synthesized and characterized. The structure elucidation for 1 performed by single crystal X-ray diffraction showed a one dimensional chain conformation in which the central copper ions arrange in a five-coordinate distorted square-pyramidal geometry. Spectroscopic titration, viscosity and electrophoresis measurements revealed that the complexes bound to DNA via an outside groove binding mode, and cleaved pBR322 DNA efficiently in the presence of ascorbate, probably via an oxidative mechanism with the involvement of ˙OH and ˙O₂⁻. Notably, the complexes exhibited considerable in vitro cytotoxicity against four human carcinoma cell lines (HepG2, HeLa, A549 and U87) with IC₅₀ values ranging from 41.68 to 159.17 μM, in addition to their excellent SOD mimics (IC₅₀ 0.091 and 0.114 μM). Besides, multispectroscopic evidence suggested their HSA-binding at the cavity containing Trp-214 in subdomain IIA with moderate affinity, mainly via hydrophobic interaction. Further, the molecular docking technique utilized for ascertaining the mechanism and mode of action towards DNA and HSA theoretically verified the experimental results.

原文链接：http://pubs.rsc.org/en/content/articlepdf/2014/dt/c3dt53577k