四氢-9-氨基吖啶的DNA嵌入特性。合成及23Na核磁共振自旋晶格弛豫时间测量。

DNA intercalating properties of tetrahydro-9-aminoacridines. Synthesis and 23Na NMR spin-lattice relaxation time measurements.

作者信息

Dinesen J, Jacobsen J P, Hansen F P, Pedersen E B, Eggert H

机构信息

Department of Chemistry, Odense University, Denmark.

出版信息

J Med Chem. 1990 Jan;33(1):93-7. doi: 10.1021/jm00163a015.

DOI:10.1021/jm00163a015

PMID:2296037

Abstract

A series of 9-(arylamino)-1,2,3,4-tetrahydroacridines, including the tetrahydro m-AMSA [N-[4-(acridin-9-yl-amino)-3- methoxyphenyl]methanesulfonamide] derivative, has been synthesized. 23Na NMR spin-lattice relaxation rate (1/T1) measurements have been used to study whether these hydrogenated acridines were capable of intercalative binding to calf thymus DNA. The results have been compared to corresponding measurements for 9-aminoacridine, m-AMSA, and MgCl2. All compounds studied were capable of intercalative binding to DNA. However, it was found that the interaction was strongly influenced by substituents on the 9-arylamino group. Thus, tetrahydro m-AMSA was found to intercalate much more weakly with DNA than m-AMSA. Removal of the 3'-methoxy substituent of the 9-arylamino group resulted in intercalation in DNA that was almost as strong as that for m-AMSA.

摘要

已经合成了一系列9-（芳基氨基）-1,2,3,4-四氢吖啶，包括四氢间-AMSA [N-[4-(吖啶-9-基氨基)-3-甲氧基苯基]甲磺酰胺]衍生物。利用23Na NMR自旋晶格弛豫率（1/T1）测量来研究这些氢化吖啶是否能够与小牛胸腺DNA进行嵌入结合。已将结果与9-氨基吖啶、间-AMSA和MgCl2的相应测量结果进行了比较。所研究的所有化合物都能够与DNA进行嵌入结合。然而，发现这种相互作用受到9-芳基氨基上取代基的强烈影响。因此，发现四氢间-AMSA与DNA的嵌入作用比间-AMSA弱得多。去除9-芳基氨基的3'-甲氧基取代基导致在DNA中的嵌入作用几乎与间-AMSA的一样强。