Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology UG and MUG, Kładki 24, Gdańsk, Poland.
Bioorg Chem. 2011 Feb;39(1):10-7. doi: 10.1016/j.bioorg.2010.11.001. Epub 2010 Nov 16.
Methylxanthines (MTX), in particular caffeine (CAF), are known as the most widely consumed alkaloids worldwide. Many accumulated statistical data indicate the protective effect of CAF intake against several types of cancer. One of the possible explanations of this phenomenon is direct non-covalent interaction between CAF and aromatic mutagen/carcinogen molecules through stacking (π-π) complexes formation. Here we demonstrate that CAF and other MTX, pentoxifylline (PTX) and theophylline (TH), form stacking complexes with carcinogenic imidazoquinoline-type (IQ-type) food-borne heterocyclic aromatic amines (HCAs). We estimated neighborhood association constants (K(AC) of the order of magnitude of 10(2)M(-1)) in neutral and acidic environment and enthalpy changes (ΔH values between -15.1 and -39.8kJ/mol) for these interactions using UV-Vis spectroscopy, calculations based on thermodynamical model of mixed aggregation and titration microcalorimetry. Moreover, using Ames test with Salmonella typhimurium TA98 strain and recently developed mutagenicity assay based on bioluminescence of Vibrio harveyi A16 strain, we demonstrated a statistically significant reduction in HCAs mutagenic activity in the presence of MTX.
甲基黄嘌呤（MTX），特别是咖啡因（CAF），被认为是世界范围内最广泛消费的生物碱。许多累积的统计数据表明，CAF 的摄入对几种类型的癌症具有保护作用。这种现象的一种可能解释是 CAF 与芳香族诱变剂/致癌剂分子通过堆积（π-π）复合物形成直接非共价相互作用。在这里，我们证明 CAF 和其他 MTX，己酮可可碱（PTX）和茶碱（TH）与致癌的咪唑并喹啉型（IQ 型）食物衍生的杂环芳香胺（HCAs）形成堆积复合物。我们使用紫外可见光谱法，基于混合聚集和滴定微量量热法的热力学模型计算，在中性和酸性环境中估计了邻位缔合常数（K（AC）数量级为 10（2）M（-1））和焓变（ΔH 值在-15.1 和-39.8kJ/mol 之间）对于这些相互作用。此外，我们使用沙门氏菌 TA98 菌株的 Ames 试验和最近开发的基于哈维弧菌 A16 菌株生物发光的致突变性测定法，证明了在 MTX 存在下 HCAs 的致突变活性有统计学意义的降低。
