Interaction between novel N-methyl-b-carboline derivatives and Bovine Serum Albumin, a typical carrier protein

F. A. O. RASSE-SURIANI; J. G. YAÑUK; S. GARCIA EINSCHLAG; M. M. GONZALEZ; R. ERRA-BALSELLS; F. M. CABRERIZO

Córdoba

Encuentro; XI Encuentro Latinoamericano de Fotoquímica y Fotobiología (XI ELAFOT); 2012

b-Carboline (bC) alkaloids belong to a family of heterocyclic compounds derived from 9H-pyrido[3,4-b]indole or norharmane (nHo) (Scheme 1). These alkaloids are widely distributed in living systems such as plants, cells, mammals, etc. In mammalian body, bCs occur as normal constituents in plasma, platelets and urine. However, under certain conditions, such as after alcohol intake and smoking, bCs basal levels (~ 0.1 nmol/l) are considerably increased (~1 nmol/l). Regarding their biological functions, a variety of significant photo-dependent roles have been described, e.g., in plants bCs could be involved in the defense response against insects (via phototoxic effects). In addition, these alkaloids are able to act as good photosensitizers, e.g., upon UV-A excitation, some bCs are able to induce DNA relaxation [1] or chromosome damage in mammalian cells [2], and also to inactivate bacteria [3] and viruses [4]. All these properties make interesting the photophysical study of bCs in different microheterogeneous environments. As it is known, in photodynamic therapy against cancer one of the forms is used photosensitizers capable of producing singlet oxygen [17], and nHo has been reported to be quite effective in producing singlet oxygen, and it could be used as an efficient cancer cell photosensitizer (18). The extent of photodynamic action depends not only on the singlet oxygen production but also on the biodistribution of the probe molecule in the cytoplasmic and mitochondrial membranes, the retention and the nature of the binding inside the cell. Thus, the binding interaction of bCs with different biosystems is important to study the net PDT efficiency. In the present work, we have investigated the interaction between a family of novel N-methyl-b-carboline derivatives, which are newly synthesized in our laboratories, whit Bovine Serum Albumin (BSA), and the pH-dependence, using fluorescence and UV-Vis spectrometry. Also we have analyzed the recorded spectra with software that uses a set of numerical techniques for the deconvolution of the absorption coefficients and the concentration profiles. Furthermore, by applying constrained regression analysis, the program provides two matrices (ST = spectra, and C = concentrations) that have physical meaning and whose matrix product reproduces the experimental matrix elements. Results may help to understand the photophysical behavior of these alkaloids in biological environments and to better assess the correlation between alkaloid prototropic forms and their biological activity.