Ma Zhidong, Rao Lu, Bierbach Ulrich
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
J Med Chem. 2009 May 28;52(10):3424-7. doi: 10.1021/jm900451y.
The reactivity of two DNA-targeted platinum-acridine conjugates with cysteine sulfur was studied. The conjugate containing an amidine-NH donor group cis to the chloride leaving group showed considerably reduced reactivity with N-acetylcysteine compared to the prototypical derivative containing a thiourea-S linkage. The opposite scenario has been observed previously in reactions with nucleobase nitrogen. Possible consequences of the unique target-selective tuning of the substitution chemistry for the pharmacodynamic properties and biological activity of these agents are discussed.
研究了两种靶向DNA的铂-吖啶共轭物与半胱氨酸硫的反应活性。与含有硫脲-S键的原型衍生物相比,含有与氯离去基团顺式的脒基-NH供体基团的共轭物与N-乙酰半胱氨酸的反应活性显著降低。此前在与核碱基氮的反应中观察到了相反的情况。讨论了这些药物取代化学的独特靶点选择性调节对药效学性质和生物活性的可能影响。