通过荧光法在不同温度下研究了2种抗癌新药:吡柔比星和表柔比星与小牛胸腺DNA的作用,分别应用荧光猝灭和荧光加强理论公式计算了它们的结合常数等,进而分别计算了它们的热力学函数.首先,热力学研究结果表明核酸与药物作用属于氢键和/或Van der Waals力;其次,即使是核酸类生物大分子其与药物的作用,荧光猝灭和荧光加强公式的计算结果仍符合等效性规律;第三,本文对这些猝灭图、双倒数图、生成常数、和热力学数据的差异进行了综合分析比较,结果表明,基于荧光加强理论公式(4)获得的图谱和数值显示更为合理.因而我们建议,即使在研究受体-底物的荧光猝灭反应时,采用荧光加强理论公式(4)可以获得更符合实际的结果.结合以前的类似结果,我们指出:对于任何生物大分子和活性小分子(含金属离子)之间由给体-受体作用所导致的荧光猝灭和荧光加强效应,均可应用我们导出的荧光加强理论公式(4)进行处理,因此我们定名其为广义的荧光猝灭方程.
A novel compound 4-methyl-7-{[4-（2,2＇：6＇,2＂-terpyridin-4＇-yl）benzyl]amino}-2H-chromen-2-one（1） was synthesized, and its DNA-binding properties, cytotoxicity, and telomerase and Topo I inhibitory activities were evaluated. For comparison, the anti-proliferative and Topo I inhibitory activities of another two analogues 2 and 3 were also investigated. Compound 1 is able to stabilize the structures of human telomere（h-tert） and promoter（c-myc and c-kit2） G-quadruplexes and h-tert i-motif. The association constants（Kb） are about 106 L/mol for h-tert G-quadruplex and/-motif, while the values are about l0s L/mol for both promoter G-qaudruplexes and calf thymus DNA（ct-DNA）. The binding of compound 1 induces the change of h-tert G-quadruplex from hybrid to antiparallel structure and exhibits 88.7% inhibition of telomerase activity at 8 μmol/L. Both compounds 1 and 3 inhibit signifi- cantly Topo I-mediated relaxation of pBR322 DNA. Compounds 1 and 2 show a high inhibitory efficacy on HepG2 and MCF-7 cancer cell lines with IC50 values of about 10^-6 mol/L. The three compounds also induce a delay of cell cycle progression. The coumarin group is vital for improving the biological activity ofterpyridine derivatives.
