Berberine structure

Other members of this sub-group, usually more closely associated with berberine in distribution, or in structure, or both, and therefore dealt with in the Berberis group, are canadine (p. 338), capaurine (p. 339), cheilanthifoline (p. 339), ophiocarpine (p. 338), sinactine (p. 338), tetra-hydroshobakunine (p. 340) and tetrahydroworenine (p. 344). 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

Keywords Berberine Palmatine Coralyne Polymorphic nucleic acid structures Alkaloid-nucleic acid interactions... 

Palmatine (Scheme 1) bears the same tetracychc structure as berberine but differs in the nature of the substituents on the benzo ring being methylene dioxy for berberine and dimethoxy for palmatine. In aqueous buffer, the UV-visible spectriun of palmatine shows maxima at 232, 268, 344.5 and 420 nm. Palmatine has a weak fluorescence spectrum in the range 400-650 nm with... 

Fig. 7 Chemical structure of berberine with atom numbering and proton labels. NMR spectra of berberine titrated with increasing concentrations of calf thymus DNA at 298 K (a) and at 350 K (b). Reprinted from [165] with permission from the publisher...

Scheme 3 Structures of berberine homodimers (Br-C2-4-Ber), Jatrorrhizine homodimers (Jat-C2-4-Jat) and berberine-Jatrorrhizine heterodimers (Ber-C2-4-Jat)...

Poly(dG-dC) poly(dG-dC) and its methylated analogue structures assume left-handed conformation (Z-DNA) in high molar sodium salt (Na", K" ), in low molar divalent cations (Ca", Mg", Ni ), micromolar concentrations of hexaamine cobalt chloride (Co(NH3)6)Cl3 and in millimolar concentrations of polyamines. In order to analyse the binding of berberine to Z-form DNA, Kumar et al. [186] reported that the Z-DNA structure of poly(dG-dC) poly(dG-dC) prepared in either a high salt concentration (4.0 M) or in 40 mM (Co(NH3)6)Cl3 remained invariant in the presence of berberine up to a nucleotide phosphate/alkaloid molar ratio of 0.8 and suggested that berberine neither bormd to Z-form DNA nor converted the Z-DNA to the... 

In order to develop compounds that can selectively target duplex RNA, Sinha et al. [ 194] studied the interaction of berberine with two different conformations of poly(rC) poly(rG) structures. Poly(rC) poly(rG) has been shown [15,215] to exist in two conformations depending on the pH of the solution, the A-form at physiological pH and the protonated form at pH 4.3. These two conformations have been characterized to have clearly defined but distinctly different circular dichroic and absorption spectral characteristics. Both the A-form and the protonated form of the RNA induced moderate hypochromic change and bathochromic shifts in the absorption maxima peaks at 344 nm and 420 nm of the alkaloid with three isosbestic points centered around 357,382 and 448 nm. Binding of berberine to both forms enhanced the fluorescence intensity, which was higher with the protonated form than with the A-from, suggesting clear differences in the nature of orientation... 

FIG. 22 Chemical structures of (a) dextromethorphan hydrobromide, (b) papaverine hydrochloride, (c) quinine hydrochloride, and (d) berberine chloride. 

Oxidation of berberine (15) with potassium ferricyanide followed by treatment with sodium hydroxide afforded oxybisberberine (130) (30%), the structure of which is still unknown (Scheme 27). The product was treated with 10% methanolic hydrogen chloride to give 8-methoxyberberinephenolbetaine (131) (93%) and 15 (77%) (88,89). Alternatively, irradiation of 15 in methanol in the presence of sodium hydroxide and Rose Bengal in a stream of oxygen gave the tetramethoxyketone 132 (59%), which was aromatized to 131 (99%) by removal of methanol on heating in methanol (90,91). 

Methoxyberberinephenolbetaine (131) possesses an interesting structural feature, namely, an 8,14-dioxygenated berberine skeleton and a masked carboxylic acid at C-8. It has been converted to phthalideisoquinoline alkaloids (Section V,D,1). Treatment of 131 with methyl iodide, hydrochloric... 

It is important to emphasize that systems in which the lone pair originates at a starred position can be represented by dipolar canonical forms as well as by purely covalent structures and that sometimes these dipolar structures are a better representation of the molecule. Examples of this are the antibiotic pyocyanine (28 29) and the berberine derivative 30+->31, 5 In... 

This is the name given to an alkaloid (mp 200-201°) isomeric with protopine, isolated from Zanthoxylum conspersipunctum Merr. (146), whose structure (157) has been confirmed by a synthesis. The reaction sequence, beginning with the corresponding berberine, was essentially that described in the original protopine synthesis (147). 

In another study, the structure-activity relationships of berberine and its derivatives were examined for their antibacterial activity. Among the 13-alkyl-substituted and the 13-unsubstituted protoberberinium salts, an increase in antibacterial activity was observed with the 13-ethyl-9-ethoxyl, the 13-ethyl, and the 13-methyl derivatives against S. aureus by eight-, four-,... 

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