Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives

Abstract

Alkaloids occupy an important position in chemistry and pharmacology. Among the various alkaloids, berberine and coralyne of the protoberberine group, sanguinarine of the benzophenanthridine group, and aristololactam-beta-d-glucoside of the aristolochia group have potential to form molecular complexes with nucleic acid structures and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights (i) the physicochemical properties of these alkaloids under various environmental conditions, (ii) the structure and functional aspects of various forms of deoxyribonucleic acid (DNA) (B-form, Z-form, H(L)-form, protonated form, and triple helical form) and ribonucleic acid (RNA) (A-form, protonated form, and triple helical form), and (iii) the interaction of these alkaloids with various polymorphic DNA and RNA structures reported by several research groups employing various analytical techniques like absorbance, fluorescence, circular dichroism, and NMR spectroscopy; electrospray ionization mass spectrometry, thermal melting, viscosity, and DNase footprinting as well as molecular modeling and thermodynamic studies to provide detailed binding mechanism at the molecular level for structure-activity relationship. Nucleic acids binding properties of these alkaloids are interpreted in relation to their biological activity.

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

“…QBAs, a group of low molecular compounds with N-heteroatom, belong to the highly bioactive substances [1]. Some side effects were reported (toxic effect on some cellular level [2][3][4][5]) in addition to the beneficial pharmacological actions (antimicrobial, antiapoptotic, antiinflamatory etc. effects [6,7]).…”

“…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.…”

“…[12][13][14][15] The exact knowledge of physico-chemical characteristics is very important for correct interpretation of experiments concerning studies of interactions and behavior of the alkaloids at nearly physiological conditions. It is evident that the study of interactions [3][4][5][6] with biologically important macromolecules (i.e., receptors, transport proteins, nucleic acids etc. ), as Amresco ® , Solon, Ohio, USA) and sodium hydroxide (reagent grade purity, Penta, Chrudim, Czech Republic) solutions were used for the pH adjustment in a pH interval pH = 2 -11 with steps ∆pH = 0.2 -0.5.…”

An important functional group, benzo[1,3]dioxole, of alkaloids induces the formation of the human telomeric DNA G-quadruplex

“…They occupy an important position in applied chemistry and also play an indispensable role in medicinal chemistry. A large number of alkaloids can form molecular complexes with nucleic acid structures, which might account for their biological activity [9].…”

Apparent circular dichroism signature of stirring-oriented DNA and drug–DNA complexes

“…Since magnitude of the LD signal is much higher than that of the CD, intercalation can be more sensitively detected in stirringoriented samples than in isotropic solution. As it is illustrated in the case of berberine [15], harmine [16] and quinacrine [17], at low drug/bp ratios DNA association of these molecules induces no detectable CD activity in isotropic solution (Fig. 3).…”