College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
DNA Cell Biol. 2012 Jun;31(6):1046-53. doi: 10.1089/dna.2011.1432. Epub 2012 Jan 25.
The interaction of calf thymus DNA (ct-DNA) with a novel synthesized pyrazolo[1,5-a]indole compound 1-methyl-7H-indeno[1,2-b]quinolinium-7-(4-dimethylamino) benzylidene triflate (MIDBT) was extensively studied by various spectroscopic techniques, viscosity measurements, and gel electrophoresis. The UV-visible observation implied that the compound interacted with ct-DNA by two binding modes, intercalating into the DNA base pairs and attaching to the helix exterior of DNA. The results of the fluorescent quenching and viscosity measurements showed that MIDBT could intercalate into DNA base pairs deeply in a classical intercalative mode. Circular dichroism results showed that the binding of MIDBT shifted ct-DNA conformation from B to A at low concentrations. In the gel electrophoresis, the compound was found to promote the cleavage of plasmid pBR 322 DNA effectively. Furthermore, cytotoxic studies of this compound against eleven selected tumor cell lines have been done. The values of 50% cytotoxic concentration (IC(50)) were in the range of 1.09-18.84 μM, exhibiting the potent cytotoxic properties.
通过各种光谱技术、粘度测量和凝胶电泳,广泛研究了小牛胸腺 DNA(ct-DNA)与新型合成的吡唑并[1,5-a]吲哚化合物 1-甲基-7H-茚并[1,2-b]喹啉-7-(4-二甲氨基)苄叉三氟甲磺酸酯(MIDBT)的相互作用。紫外-可见观察表明,该化合物通过两种结合模式与 ct-DNA 相互作用,即嵌入 DNA 碱基对和附着在 DNA 螺旋外。荧光猝灭和粘度测量的结果表明,MIDBT 可以以经典的嵌入模式深入嵌入 DNA 碱基对。圆二色性结果表明,在低浓度下,MIDBT 的结合将 ct-DNA 构象从 B 型转变为 A 型。在凝胶电泳中,发现该化合物能有效地促进质粒 pBR 322 DNA 的断裂。此外,还对该化合物对 11 种选定的肿瘤细胞系的细胞毒性进行了研究。50%细胞毒性浓度(IC(50))值在 1.09-18.84 μM 范围内,表现出很强的细胞毒性。