Wadkins R M, Graves D E
Department of Chemistry, University of Mississippi, University 38677.
Nucleic Acids Res. 1989 Dec 11;17(23):9933-46. doi: 10.1093/nar/17.23.9933.
The equilibrium binding of the antitumor agent m-AMSA and its biologically inactive analog o-AMSA to native and synthetic DNAs are compared over a wide range of ionic strengths and temperatures. Although o-AMSA binds DNA with a higher affinity than m-AMSA it is not effective as an antitumor agent. Both m-AMSA and o-AMSA bind DNA in an intercalative manner. Indepth investigations into the thermodynamic parameters of these interactions reveal the interaction of m-AMSA with DNA to be an enthalpy driven process. In contrast, the structurally similar but biologically inactive o-AMSA binds DNA through an entropy driven process. The differences in thermodynamic mechanisms of binding between the two isomers reveal that the electronic and/or steric factors resulting from the position of the methoxy substituent group on the anilino ring directs the DNA binding properties of these compounds and ultimately the biological effectiveness as an antitumor agent.
在广泛的离子强度和温度范围内，比较了抗肿瘤药物间-甲氧基-蒽二胺（m-AMSA）及其无生物活性的类似物邻-甲氧基-蒽二胺（o-AMSA）与天然和合成DNA的平衡结合情况。尽管o-AMSA与DNA的结合亲和力高于m-AMSA，但它作为抗肿瘤药物并不有效。m-AMSA和o-AMSA均以嵌入方式结合DNA。对这些相互作用的热力学参数进行深入研究表明，m-AMSA与DNA的相互作用是一个由焓驱动的过程。相比之下，结构相似但无生物活性的o-AMSA通过熵驱动过程结合DNA。两种异构体结合的热力学机制差异表明，苯胺环上甲氧基取代基位置所产生的电子和/或空间因素决定了这些化合物的DNA结合特性，并最终决定了其作为抗肿瘤药物的生物学有效性。
