Routier S, Bernier J L, Catteau J P, Riou J F, Bailly C
Laboratoire de Chimie Organique Physique, URA 351 CNRS, USTL C3, Villeneuve d'Ascq, France.
Anticancer Drug Des. 1998 Jul;13(5):407-15.
Two anthraquinone derivatives of the anticancer drugs mitoxantrone and ametantrone were examined for their ability to bind to DNA and to modulate the formation of topoisomerase-DNA cleavable complexes in vitro. The guanidinium groups introduced at the termini of the two aminoethylamino side chains of mitoxantrone can reinforce the interaction with DNA as judged from thermal denaturation studies with calf thymus DNA and polynucleotides. Footprinting experiments indicate that the binding to DNA of compound SR107 lacking the 5,8-hydroxyl substituents is essentially nonspecific whereas its congener SR 103 interacts preferentially with GC-rich sequences, particularly those containing 5'-(A/T)CG sites. Compound SR103, which bears two hydroxyl groups on the anthraquinone chromophore, promotes the cleavage of DNA by topoisomerase II and is cytotoxic toward human KB carcinoma cells in vitro. In contrast, the analogue SR107, which lacks OH groups, has no effect on topoisomerase II and is not cytotoxic.
对两种抗癌药物米托蒽醌和氨茴米托蒽醌的蒽醌衍生物进行了研究，考察它们在体外与DNA结合以及调节拓扑异构酶-DNA可裂解复合物形成的能力。从小牛胸腺DNA和多核苷酸的热变性研究判断，在米托蒽醌两个氨乙基氨基侧链末端引入的胍基可增强与DNA的相互作用。足迹实验表明，缺少5,8-羟基取代基的化合物SR107与DNA的结合基本上是非特异性的，而其同系物SR 103则优先与富含GC的序列相互作用，特别是那些含有5'-(A/T)CG位点的序列。在蒽醌发色团上带有两个羟基的化合物SR103可促进拓扑异构酶II对DNA的切割，并且在体外对人KB癌细胞具有细胞毒性。相反，缺少OH基团的类似物SR107对拓扑异构酶II没有影响，也没有细胞毒性。
