Sanguinarine structure

This sub-group includes four alkaloids, a-homochelidonine, chelidonine, chelerythrine, and sanguinarine, whose nuclear structure and interrelationships (formula I to IV) have been established. Three minor chelidonium alkaloids, oxychelidonine, methoxychelidonine and oxy-sanguinarine, whose association is implied by their names, are included. 

In addition to the study of the bis-benzo[c]phenanthridines just discussed above, Marek and coworkers have also extensively studied other benzojcjphenanthridine alkaloids [111,121]. The structures of the alkaloids for which data have been reported and their respective chemical shifts are collected in Figure 14.12. These alkaloids include the methyl chloride salts, sanguinarine chloride (110), chelrythine chloride (111), sanguilutine chloride (112) and chelirubine chloride (113). 6-Substituted and... 

The structure of 33 has been supported by using elemental analysis, mass spectrometry and NMR spectroscopy [119]. However, the NMR spectra provided a more complex depiction. They indicated the presence of five species in a CDCI3 solution of sanguinarine fi ee base (I) a major bimole-cular stereoisomer, the racemate 6R,6"R + 6S,6 S, vsdiich is thermodynamically voured according to AMI calculations [120] (II) a minor isomer, a... 

A range of alkaloids including isoquinoline, indolizidine, benzazepine, oxazine, quinoline and indole alkaloids were examined as potential inhibitors of eukaryote protein kinases such as PKC, MLCK and PKA. Only three oxazine alkaloids and four isoquinoline-based alkaloids and inhibitors of the protein kinases tested. A narrow structural and protein kinase target specificity, was observed. (+)-Boldine (39) and bulbocapnine (40) are specific for MLCK, while apomorphine (41) and sanguinarine (42) are for PKA. 

Table 6 summarizes the results of alkaloid isolation studies. The structure of the new alkaloid bocconine (239) from Bocconia cordata was deduced mainly on the basis of n.m.r. studies.231 The c/D-ring substitution pattern was indicated by comparison of its n.m.r. spectrum with those of sanguinarine and chelery-thrine. The downfield shift of the C(11)-H by 0.67 p.p.m. in 5,6-dihydrobocconine... 

Punctatine, a phenolic QBA of the sanguinarine type, has been isolated from Z. punctatum Vahl. [48], The suggested structure contains three methoxy groups and one hydroxyl in unknown positions. 

Chelerythrine is a potent inhibitor of protein kinase C [140], and an enormous number of papers from this area are now available. Sanguinarine and chelerythrine are the first non-peptide species to exhibit affinity for rat liver vasopresin Vi receptors [141]. A novel synthetic QBA of the structure 3, coded NK 109, has shown notable anti-tumour effects against several drug-resistent human tumour cells [142,143],... 

When sanguinarine nitrate is oxidized in alkaline solution with potassium ferricyanide it is converted into oxysanguinarine, a neutral compound whose structure is represented by XIX. It proved to be identical with a substance obtained from the crude mixture of Sanguinaria alkaloids (40) by a process involving chromatography. 

Benzylisoquinoline is the structural backbone of many alkaloids that possess potent therapeutic properties. Benzylisoquinoline alkaloids (BIAs) include the narcotic analgesics codeine and morphine, the antimicrobials sanguinarine and berberine, the anti-tussive and anticancer agent noscapine, and the muscle relaxants papaverine and tubocurarine. 

Other responses, such as formation of phytoalexins, are more specific (Chappell and Hahlbrock, 1984 Luckner, 1980). It has been shown that production of secondary compounds in cell cultures also can be enhanced by environmental stress. Treatment of cell cultures with fimgal, bacterial, or plant cell wall materials often results in the formation of a number of flavonoids, stilbenes, terpenoids, anthraquinones, rutacridone alkaloids, sanguinarine, and gossypol (Eilert, 1987 Heinstein 1985). In some cases, production of these metabolites is transient. Clearly, we need more information on the basic principles of the defensive response, such as structures and perception of defensive signals, transduction, and translation of these signals into a response (Luckner, 1980 Wink, 1987). 

Sanguinarine is not derived from chelidonine. Rather, both alkaloids have a common precursor represented by structure 26. 

Fig. 36.3 Chemical structures of sanguinarine and coptisine and CZE separation of seven alkaloids in an extract of Chelidonium majus L. Peaks (7) sanguinarine, (2) coptisine, (3) chelerythrine, (4) stylopine, (5) chelidtmme, (6) protopine, (7) allocryptopine, and (x) unknown component. Conditions 20 mM phosphate buffer, pH 3.1. Separation capillary 75 pm, i.d. uncoated fused silica, 50 cm in length (40 cm effective length). Applied voltage 16 kV. Light-emitting-diode-induced fluorescence (LED) excitation wavelength 280 nm (Modified from reference [14])...

Like tubocurarine, the quartemary benzo-phenanthridine sanguinarine is absorbed badly. It reacts with negatively charged and nucleophihc groups of proteins and inhibits several enzymes, e.g., Na /K -ATPase (Straub and Carver, 1975). In addition, it intercalates DNA due to its planar structure (Nandi and Maiti, 1985). 

Aiyai VN, Benn MH, Hanna T, Jacyno J, Roth SH, Wilkens JL (1979) The principal toxin of Delphinium brownii and its mode of action. Experientia 35 1367-1368 Chappie DJ, Clark JS (1983) Pharmacological action of breakdown products of atracurium and related substances. Br J Anaesth 55 Suppl 1 IIS Cohen HG, Seifen EE, Straub KD, Tiefenback C, Stermitz FR (1978) Structural specificity of the NaK-ATPase inhibition by sanguinarine. Biochem Pharmacol 27 2555 Dolejs L, Hanus V (1967) Mass spectrometry of rhoeadine type alkaloids. Tetrahedron23 2997 Horn AS, Rodgers JR (1976) Structural and conformational relationships between the opiates. Nature (London) 260 795-797... 

---