Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran.
DNA Cell Biol. 2012 Jan;31(1):122-7. doi: 10.1089/dna.2011.1228. Epub 2011 Jul 1.
One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. In recent years, some researchers have shown that antiviral drugs, such as ritonavir, saquinavir, and nelfinavir, inhibit the growth of over 60 cancer cell lines derived from nine different tumor types. This article studied the anticancer potential of an antiviral drug, lamivudine (LA). The interaction of LA and calf thymus DNA (CT-DNA) was studied using emission, absorption, circular dichroism (CD), and viscosity techniques. The binding constants evaluated from fluorescence data at different temperatures revealed that fluorescence enhancement is a static process that involves complex-DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed ΔH<0 (-126.38±0.61 kJ mol(-1)) and ΔS<0 (-352.17±2.1 J mol(-1) K(-1)); therefore, van der Waals interactions or hydrogen bonds are the main forces in the binding of LA to CT-DNA. The values of K(f) clearly underscore the high affinity of LA to DNA. In addition, detectable changes in the CD spectrum of CT-DNA in the presence of LA indicated conformational changes. All these results showed that groove binding is the binding mode of this drug and CT-DNA.
一种加速新型癌症药物上市的方法是将已批准用于其他疾病的药物作为抗癌药物进行测试。近年来，一些研究人员发现，抗病毒药物，如利托那韦、沙奎那韦和奈非那韦，能够抑制 9 种不同肿瘤类型的 60 多种癌细胞系的生长。本文研究了抗病毒药物拉米夫定（LA）的抗癌潜力。使用荧光发射、吸收、圆二色性（CD）和粘度技术研究了 LA 与小牛胸腺 DNA（CT-DNA）的相互作用。不同温度下荧光数据评估的结合常数表明，荧光增强是一个静态过程，涉及基态下的复合物-DNA 形成。此外，药物与 CT-DNA 之间反应的焓变和熵变表明 ΔH<0（-126.38±0.61 kJ mol(-1)）和 ΔS<0（-352.17±2.1 J mol(-1) K(-1)）；因此，范德华相互作用或氢键是 LA 与 CT-DNA 结合的主要作用力。K(f)的值清楚地强调了 LA 与 DNA 的高亲和力。此外，在 LA 存在下 CT-DNA 的 CD 光谱发生可检测的变化表明构象发生了变化。所有这些结果表明，沟结合是该药物与 CT-DNA 的结合模式。
