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Caffeine, pentoxifylline and theophylline form stacking complexes with IQ-type heterocyclic aromatic amines

Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology UG and MUG, Kładki 24, Gdańsk, Poland.
Bioorganic Chemistry (Impact Factor: 2.14). 02/2011; 39(1):10-7. DOI: 10.1016/j.bioorg.2010.11.001
Source: PubMed

ABSTRACT 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.

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    • "Fig. 2 contains the biological data recalculated into A D units according to Eq. (1), and the A D (y 0 ) dependence computed from Eqs. (2) and (3) under the sole action of the interceptor mechanism (i.e. K YN ¼0) (the magnitudes of the complexation parameters were taken from Woziwodzka et al. (2011) and the estimated magnitude of the IQ- DNA binding was taken as K XN ¼2970 M À 1 from Sartorius and Schneider (1997)). Small variation of the binding parameters within 10% range enabled to achieve very good fitting of experimental data (solid line in Fig. 2) suggesting that the IQ- CAF systems follow the interceptor mechanism in the same way as the IQ-CHL systems discussed above. "
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    Journal of Theoretical Biology 06/2014; 357. DOI:10.1016/j.jtbi.2014.06.016 · 2.30 Impact Factor
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    • "However, the continuous introduction of caffeine may cause subtle effects acting as a pseudo-persistent pollutant for its continuous release in the environment and little is known about its chronic effects (OECD, 2002). Furthermore, several studies reported the genotoxic potential and mutagenic potential of caffeine on animal models and results are inconsistent and inconclusive (Choundhury and Palo, 2004) even if caffeine showed antigenotoxic activity towards known genotoxins (Woziwodzka et al., 2011). "
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    • "This mechanism of protection is known as " interceptor " mode of CAF and other methylxanthines action and was proposed by Bedner et al. [19]. The " interceptor " mode of CAF was described and analyzed for HCAs [15] and several other aromatic compounds: ethidium bromide [20] [21], propidium iodide [19] [20], quinacrine mustard, ICR170, ICR191 [22], proflavine [23], and several anticancer drugs [17] [24] [25]. Similar mechanism was also described for interaction of chlorophyllin (CHL) [26] and other natural constituents of human diet [27] with several aromatic compounds. "
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