Hammud Hassan H, Nemer Georges, Sawma Walid, Touma Jhonny, Barnabe Pascale, Bou-Mouglabey Yolla, Ghannoum Amer, El-Hajjar Jida, Usta Julnar
Beirut Arab University, Department of Chemistry, Beirut, Lebanon.
Chem Biol Interact. 2008 May 28;173(2):84-96. doi: 10.1016/j.cbi.2008.03.005. Epub 2008 Mar 21.
A series of adenine-copper complexes (1-6) with various ligands (Cl(-), SCN(-), BF(4)(-) and acac [acetylacetonate ion]) have been synthesized and characterized by elemental analysis, infrared spectroscopy and thermal analysis. Among the six complexes only complex (1), Cu(2)(adenine)(4)Cl(4).2EtOH (abbreviated as Cu-Ad), demonstrated some toxic effect on different cell lines. In vitro investigations of the biological effect of Cu-Ad complex have shown that it: (1) binds genomic DNA; (2) decreases significantly, the viability of cells in culture in a concentration (15-125 microM)-dependant manner; an estimated IC(50) of: 45 microM with HepG2; 73 microM with C2C12; 103 microM with NIH3T3; and 108 microM with MCF7. Cu-Ad had no effect on A549 cells; (3) inhibits Taq polymerase-catalyzed reaction; (4) inhibits the binding of the transcription factor GATA-5 to labeled DNA probes; (5) inhibits mitochondrial NADH-UQ-reductase with an estimated IC(50) of 2.8 nmol, but had no effect on succinate dehydrogenase activity; (6) increases reactive oxygen species (60%) at 45 microM Cu-Ad; and (7) decreases ATP (80%) at 50 microM Cu-Ad. The new compound Cu(2)(adenine)(4)Cl(4).2EtOH (Cu-Ad), belongs to a class of copper-adenylate complexes that target many biochemical sites and with potential anti-cancer activity.
一系列含有不同配体（Cl⁻、SCN⁻、BF₄⁻和acac [乙酰丙酮离子]）的腺嘌呤 - 铜配合物（1 - 6）已被合成，并通过元素分析、红外光谱和热分析进行了表征。在这六种配合物中，只有配合物（1），即Cu₂(腺嘌呤)₄Cl₄·2EtOH（简称为Cu - Ad），对不同细胞系表现出一定的毒性作用。对Cu - Ad配合物生物效应的体外研究表明，它：（1）结合基因组DNA；（2）以浓度（15 - 125 μM）依赖的方式显著降低培养细胞的活力；估计的半数抑制浓度（IC₅₀）为：对HepG2细胞为45 μM；对C2C12细胞为73 μM；对NIH3T3细胞为103 μM；对MCF7细胞为108 μM。Cu - Ad对A549细胞无影响；（3）抑制Taq聚合酶催化的反应；（4）抑制转录因子GATA - 5与标记DNA探针的结合；（5）抑制线粒体NADH - UQ还原酶，估计的IC₅₀为2.8 nmol，但对琥珀酸脱氢酶活性无影响；（6）在45 μM Cu - Ad时使活性氧增加（60%）；（7）在50 μM Cu - Ad时使ATP减少（80%）。新化合物Cu₂(腺嘌呤)₄Cl₄·2EtOH（Cu - Ad）属于一类靶向多个生化位点且具有潜在抗癌活性的松果体素配合物。
