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

RASSE-SURIANI; FEDERICO A; YAÑUK, JUAN G; GARCIA EINSCHLAG, FERNANDO S; GONZÁLEZ, MARÍA M; ERRA-BALSELLS, ROSA; CABRERIZO, FRANCO M

Encuentro; XI ELAFOT; 2012

β-carboline (βCs) 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 [1], insects [2], mammals [3], etc. In mammalian body, βCs occur as normal constituents in plasma, platelets and urine. However, under certain conditions, such as after alcohol intake and smoking, βCs basal levels (~ 0.1 nmol/l) are considerably increased (~ 1 nmol/l) [4]. Regarding their biological functions, a variety of significant photo-dependent roles have been described, e.g., in plants βCs could be involved in the defense response (via phototoxic effects). In addition, these alkaloids are able to act as good photosensitizers, e.g., upon UV-A excitation, some βCs are able to induce DNA relaxation [5] or chromosome damage in mammalian cells [6], and also to inactivate viruses [7]. All these properties make interesting the photophysical study of βCs in different microheterogeneous environments. As it is known, 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 βCs with different biosystems is important to study the net photodynamic efficiency. In the present work, we have investigated the pH dependence on the interaction between a family of novel N-methyl-β-carboline derivatives (table), recently synthesized in our laboratories, and Bovine Serum Albumin (BSA), by fluorescence emission and UV-Vis spectroscopy. Data analysis was performed with a series of matrix techniques for the deconvolution of spectra and concentration profiles. Furthermore, by applying the constrained regression analysis, we obtained two matrices (ST = spectra, and C = concentrations) that have physical meaning and whose matrix product reproduces the experimental matrix elements. Results may help us 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.