Capillary zone electrophoretic studies of interactions of some quaternary isoquinoline alkaloids with DNA constituents and DNA

Abstract

Capillary zone electrophoresis was applied for the investigation of interactions of some quaternary isoquinoline alkaloids, namely sanguinarine, chelerythrine, berberine, and jatrorrhizine, with DNA constituents and with DNA. None of these alkaloids attach covalently to nucleotides or to the whole DNA under physiological conditions. The interaction with DNA constituents is a noncovalent complexation based on weak intermolecular forces. Electrostatic attraction participates in the interaction but other types of intermolecular forces are involved as well. Cations were identified as the most probable interacting forms of the alkaloids. The interaction with compounds derived from purine was always stronger than those derived from pyrimidine. All alkaloids behaved analogously and similarly to ethidium bromide, the classic DNA intercalator. Stability constants K (in l.mol(-1)) for sanguinarine and chelerythrine in phosphate buffer of pH 7.4 (I(S) = 30 mM) ranged from tens to hundreds.

Spectrophotometric study of time stability and acid-base characteristics of chelerythrine and dihydrochelerythrine

“…This study points out that the behavior of chelerythrine and especially its dihydro-derivative in aqueous solutions is more complex than be expected [7,8,10,11].…”

“…Many very extraordinary properties were observed in the frame of detail studies of acidobasic and electrophoretic behavior of sanguinarine (SA) and chelerythrine (CHE) [8][9][10][11] and mainly their dihydroderivatives (dihydrochelerythrine, dihydrosanguinarine, etc., the former being recognized as the first metabolite of detoxification of sanguinarine in rats [2]) in the presence of inert electrolytes [3,4,10,11]. They exhibit very characteristic spectral features that can be used for their direct determination, for studies of their interactions with biomacromolecules using UV-VIS spectrophotometry, fluorimetry, mass spectrometry etc.…”

Acid-base behaviour of sanguinarine and dihydrosanguinarine

“…The reported pK R+ values of SA (7.32 -8.16) [8,9,11,[15][16][17][18][19][20][21][22] and our previous experience with electrophoretic behaviour of SA [20,23] imply that at least some of the published pK R+ values are distorted by the abovementioned experimental conditions. Thus, in some cases an organic solvent was added to the solutions to improve the alkaloid solubility.…”

“…Different behaviour and solubility of SA in different media, which were adjusted to identical pH and ionic strength, must result from interactions of ionic species of acids and/or bases with investigated alkaloids. Recently we have found that MOPS and CAPSO anions form pseudo-micelles that can enhance dissolution of uncharged SA [23,26]. It has to be therefore expected that analogical interaction occurs between uncharged hydrophobic sanguinarine not only with complex molecular structures but similarly with the components of buffer solutions, electrolytes and non-electrolytes and other compounds present in solutions etc.…”

Conventional protein kinase C isoenzymes undergo dephosphorylation in neutrophil-like HL-60 cells treated by chelerythrine or sanguinarine

“…1) interact with proteins and DNA (Walterová et al 1995;Vlčková et al 2005). Similarly to other PKC inhibitors, which are known to inhibit oxidative burst activated by both receptor-mediated and receptorindependent mechanisms (Twomey et al 1990), sanguinarine appeared to attenuate oxidative burst stimulated with cytochalasin B/fMLP (Ferrandiz et al 1991) or PMA (Agarwal et al 1991) in rat and human neutrophils, respectively.…”