Protoberberine alkaloids pharmacology

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. 

Xylopinine. Among many popular protoberberine alkaloids, xylopinine has been of interest to synthetic chemists because of its pharmacological activity (112). Three groups (21,23,29-32,44,107) have independently described total synthesis of this alkaloid Ninomiya et al. (16) and Kametani et al. (66) succeeded in the asymmetric synthesis of this alkaloid by enamide photocyclization. 

Iwasa, K. The biotransformation of protoberberine alkaloids by plant tissue cultures. In The Alkaloids Chemistry and Pharmacology Cordell, G.A., Ed. Academic Press San Diego, CA, 1993 46, 273-346. 

Most protoberberine alkaloids occur in nature as tetrahydroprotober-berines or as quaternary protoberberinium salts. However, in the last few years a number of quaternary iV-methyltetrahydroprotoberberine salts as well as 7V-oxides have been reported. In addition to the usual substitution pattern, the C-8 position may bear a methyl group as in the naturally occurring protoberberine alkaloid ( —)-corytenchirine. Two recently reported retroprotoberberines are TV-methyl- and iV,(9-dimethylmecambridine the chemistry, synthesis, pharmacology, and biogenesis of the protoberberine alkaloids have been reviewed. 

The pharmacological investigations being carried out with the protoberberine alkaloids have been showing, as the years advance, a growing and relevant number of very important biological activities. 

Based on the data compiled between 1986 and 2001, one can effectively observe that very simple living systems, such as bacteria and fungi, and more complex organic systems, have shown susceptibility to the diverse biological activities exercised by the protoberberine alkaloids. This fact denotes the number of possibilities that can arise in the near future for the utilization of this class of alkaloids as tools to benefit health care, in the area of experimental pharmacology, or even as preventive or curative therapeutic agents. 

The known chemistry of the Annonaceae is mainly based on the work of Cave and Leboeuf on the benzyhsoquinoline alkaloids. After this work, several papers were published which evidenced the presence of alkaloids derivatives of isoquinolines. Approximately 800 alkaloids of the types isoquinolines, protoberberine, aporphine, and others were isolated from different genera of the Aimonaceae. Previous chemical and pharmacological investigations have indicated that bisbenzylisoquinolines are important bioactive components existing in plants of the Annonaceae family. Other terpenes, flavonoids, Hgnans, acetogenins, and some aromatic compounds are also found in the family but the alkaloids are the major chemical constituents. 

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