Anthraquinones from rubiaceae

In regard to the antineoplastic potentials of Rubiaceae, some evidence has already been presented that clearly demonstrates that anthraquinones inhibit the enzymatic activity of topoisomerase II. An example of antineoplastic anthraquinones that target topoisomerase II is mitoxantrone (Novatrone ), which is currently approved for clinical use in the United States (16). In the Pacific Rim, about 150 species of plants classified within the family Rubiaceae are medicinal, of which Prismatomeris albidiflora, Krtoxia valeriartoides, Damnacanthus indicus, and Morinda umbellata are known to produce anthraquinones. An interesting development from Rubiaceae would be to investigate its members for anthraquinones and assess them for topoisomerase inhibitors. The discovery of inhibitors of topoisomerase II of clinical antineoplastic value can be reasonably expected. 

RPLC separation with spectrophotometric detection is often applied to the identification of the anthraquinone colour components of cochineal, lac dye and madder. [28,40,41,50 53] In particular the latter, containing many colourants, is the object of many research studies. Due to the large number of anthraquinones isolated from plants of the Rubiaceae family, their unambiguous identification solely by UV-Vis detection is not always possible,... 

Damnacanthol-3-0-(3-D-primeveroside (203) and lucidin 3-0-P-D-primeveroside (204), two anthraquinone isolates from -butanol soluble phase of the methanol extract of Morinda citrifolia L. (family Rubiaceae) roots, were evaluated to demonstrate a significant reduction of the blood glucose levels (p < 0.05) at 5 h after oral administration (100 mg/kg/body-weight). ... 

Anthraquinones are found extensively in various plant species, especially from the families Liliaceae, Polygonaceae, Rhamnaceae, Rubiaceae and Fabaceae. They are also biosynthesized in micro-organisms, e.g. Penicillium and Aspergillus species. The following structural variations within anthra-quinone aglycones are most common in nature. 

Red natural anthraquinone dyes on ancient textile materials can be readily identified by thin-layer chromatography (TLC) if they belong to the class of madder dyes. The method also shows which type of dye plant from the family Rubiaceae has been used for dyeing (Rubia tinctorum L., R. peregrina L.,... 

ABSTRACT This paper attempts to present a review on the study of phytochemical and pharmacological activities of plants from the genus Hedyotis (Rubiaceae) in the last seven decades, which include our work on Malaysian Hedyotis species. The structure-activity relationships of compounds isolated from this genus are compiled and discussed. Finally, there is also a brief discussion on the biosynthesis of anthraquinones, iridoid glycosides and alkaloids, which are the common constituents of Hedyotis species. 

Rubiaceaous plants are usually rich in anthraquinones. The first four anthraquinones, 2-methyl-3-methoxyanthraquinone (7), 2-methyl-3-hydroxyanthraquinone (8), 2-methyl-3-hydroxy-4-methoxyanthraquinone (9) and 2,3-dimethoxy-6-methylanthra-quinone (10) reported in genus Hedyotis were isolated from H. diffusa [26]. All the compounds except for (10) are substituted only in ring C. The structure of (10) has been later confirmed by synthesis based on Diels-Alder reaction. This anthraquinone has been the only one reported from a natural source until today. Other anthraquinones possessing the same substitution pattern are synthetic products [27]. 

The biogenetic studies on anthraquinones, iridoids and alkaloids discussed here mostly represent a general biosynthetic pathway for the Rubiaceae family. Despite the relatively large number of new compounds reported from only 13 species, the biosynthetic pathways for the new compounds of this genus are seldom elaborated. 

Quinones, naphthoquinones, and anthraquinones are found in many types of higher plants and fungi. About 600 naturally occurring quinones have been described. More than half of these are from one plant family, the Rubiaceae (Has-1am, 1974 Harbome, 1982). Quinones are cyclic a,(3-dike-tones of such a structure that they are converted by reduction into hydroquinones, that is, phenols containing two hydroxyl groups such as (2) (Fig. 6.1) (Morrison and Boyd, 1973). The reduced and oxidized forms are closely balanced energetically and are easily interconverted. 

As is true for the naphthoquinones, anthraquinones are synthesized by a variety of routes in plants and fimgi (Pack-ter, 1980). Most are derived from either acetate-malonate or isochorismate-a-ketoglutaric acid-mevalonate pathways. Anthraquinones also are produced frequently in plant tissue cultures (Ellis, 1988). Tissue cultures of Cinchona species (Rubiaceae) produce at least 30 different anthraquinones. 

Anthraquinones in which only one ring is substituted are particularly common in the Bignoniaceae, Rubiaceae, and Verbenaceae, but do not appear to occur in fungi, the Poly-gonaceae, Rhamnaceae, Fabaceae, Caesalpinioideae, or the Liliaceae (A/oe). These compounds are derived from a pathway similar to that previously discussed for naphthoquinones, but with subsequent addition of mevalonate-derived units (Fig. 6.8). 

Phylloquinone (37), plastoquinone, ct-tocopherol, and ubiquinone (13) (Fig. 6.2) are produced by a cell suspension culture from Morinda lucida (Rubiaceae). Changes in environmental, hormonal, and other cultural conditions result in accumulation of anthraquinones in cultures of Galium, Morinda, diXidRubia (all Rubiaceae). The addition of o-succi-nylbenzoic acid (38) causes an increase in the amount of anthraquinones produced. 2-Carboxy-4-oxotetralone (43) or l,4-dihydroxy-2-naphthoic acid (40) appear to be intermediates in the synthesis of both anthraquinones and phylloqui-nones. 

Fig, 6.15. Proposed biosynthesis of anthraquinones in species of Rubiaceae (modified from Inouye and Leismer, 1988 used with permission of the copyright owner, John Wiley Sons, Ltd., Chichester). 

Anthraquinones derived from shikimic and isochorismic acid are known to occur only in certain dicotyledonous families Bignoniaceae, Gesneriaceae, Rubiaceae, Scrophulariaceae, and Verbenaceae (Gentianales, Lamiales, and Scro-phulariales). These families also characteristically accumulate iridoid monoterpenes (Dahlgren et al., 1981). 

Pseudopurpurin, 1,2,4-trihydroxyanthraquinone-3-carboxylic acid, is one of the main anthraquinones, along with pupurin and alizarin, foimd in madder (qq.v) derived from Rubia tinctorum L. and many other plants of the Rubiaceae including Gallium and Relbunium species. It is selectively extracted and used for... 

Purpurin, 1,2,4-trihydroxyanthraquiiione, is an anthraquinone foimd in association with alizarin and pseudopnrpurin in dyestuffs derived from various Rubiaceae ( madder ) species therefore a common component of lake pigments produced from them. It is also produced synthetically and may be used for so-called aHzarin violet . The synthetic form is hsted in the Colour Index (1971) as Cl 58205, the natural form as Cl 75410. 

This review has been written in order to update the literature on anthraquinones occurring in the Rubiaceae. Since appearance of the excellent book on naturally-occurring quinones by R.H. Thomson 120) in 1971 about 50 new anthraquinones have been isolated from members... 

Table 8. List of Species of the Rubiaceae Reported to Contain Anthraquinones and the Anthraquinones Isolated from Them ...

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