Nagle Padraic S, Rodriguez Fernando, Kahvedzić Amila, Quinn Susan J, Rozas Isabel
School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
J Med Chem. 2009 Nov 26;52(22):7113-21. doi: 10.1021/jm901017t.
In this paper we report the synthesis of three families of new amidine-based aromatic derivatives as potential DNA minor groove binding agents for the treatment of cancer. The preparation of monoguanidine, mono-2-aminoimidazoline, and asymmetric diphenylguanidine/2-aminoimidazoline derivatives (compounds 1a-c to 8a-c) is presented. The affinity of these substrates and of a family of mono- and bis-isoureas (previously prepared in Rozas' laboratory) for DNA was evaluated by means of DNA thermal denaturation measurements. In particular, compounds 2c, 5c, 6c, 7c, and 8c were found to bind strongly both to natural DNA and to adenine-thymine oligonucleotides, showing a preference for the adenine-thymine base pair sequences.
在本文中，我们报道了三类新型脒基芳香族衍生物的合成，它们作为潜在的DNA小沟结合剂用于癌症治疗。文中介绍了单胍、单-2-氨基咪唑啉以及不对称二苯基胍/2-氨基咪唑啉衍生物（化合物1a - c至8a - c）的制备方法。通过DNA热变性测量评估了这些底物以及一类单异脲和双异脲（先前在罗萨斯实验室制备）与DNA的亲和力。特别地，发现化合物2c、5c、6c、7c和8c与天然DNA和腺嘌呤 - 胸腺嘧啶寡核苷酸都有强烈的结合，对腺嘌呤 - 胸腺嘧啶碱基对序列表现出偏好。
