Plant-derived anthraquinones

The phenolics include anthocyanins, anthraquinones, benzofurans, chromones, chromenes, coumarins, flavonoids, isoflavonoids, lignans, phenolic acids, phenylpropanoids, quinones, stilbenes and xanthones. Some phenolics can be very complex in structure through additional substitution or polymerization of simpler entities. Thus xanthones can be prenylated and flavonoids, lignans and other phenolics can be glycosylated. Condensed tannins involve the polymerization of procyaninidin or prodelphinidin monomers and hydrolysable tannins involve gallic acid residues esterified with monosaccharides. As detailed in this review, representatives of some major classes of plant-derived phenolics are potent protein kinase inhibitors. 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

Anthraquinone glycosides have long been used medicinally as cathartics and laxatives. Plant-derived drugs of this type include aloes Aloe species), cascara sagrada (Rhamnus purshiams), frangula (Rhamnus frangula), rhubarb (Rheum officinale), rumex or yellow dock (Rumex crispus) and senna (Cassia spp.). Many of the commercial preparations (patent medicines) based on these plants are readily available. 

Anthraquinone dyes are derived from several key compounds, ie, dye intermediates. Production of these dye intermediates often requires sophisticated production processes and a large amount of investment in plant constmction. The competitiveness of final products, dyestuffs, depends on that of the intermediates, ie, quaUty, cost, and availabiUty. 

Borges WdS, Pupo MT, Novel anthraquinone derivatives produced hy Phoma sorghina, an endophyte found in association with the medicinal plant Tithonia diversifolia (Asteraceae),Chem Soc 17 929-934, 2006. 

Dimeric anthraquinone and their derivatives are also present as aglycones in anthraquinone glycoside found in the plant kingdom. 

Several studies published since March 1996 have expanded the list of in vitro integrase inhibitors effective at IC50 values below 100 pM. These include two dicaffeoylquinic acids obtained from medicinal plants and a synthetic analog, L-chicoric acid [68], the HIV protease inhibitors NSC 117027 and NSC 158393 [69], certain anthraquinone derivatives [70], coumermycin, and pyridoxal phosphate [71]. In addition to exhibiting in vitro inhibition, the dicaffeoylquinic acids effectively inhibited HIV-1 replication in T-lymphoblastoid cell lines [68]. 

Xanthones in higher plants are also formed by this mixed pathway, though the polyketide chain originates from a benzoic acid instead of the usual cinnamic acid. Cyclization now affords a benzophenone (691), rather than a chalcone, which subsequently cyclizes to the xanthone, a route used with considerable success in the laboratory (Scheme 280). Other xanthones are derived only from acetate, through ring opening, decarboxylation and cyclization of an anthraquinone precursor. 

The fiber is first treated with metal salts (mordanted). Highly adhesive, basic metal compounds are formed on the fiber. These compounds are capable of producing insoluble colored complexes (lakes) with certain azo and anthraquinone derivatives. Alizarin is the best-known anthraquinone derivative for this process (see Section 2.3). It used to be isolated from the root of the madder plant but has now been replaced by the synthetic product. Suitable azo dyes contain, e.g., hydroxyl or carboxyl groups in the position ortho to the azo group on one or both of the aromatic nuclei. The shade of the dyeing depends on the type of metallic mordant used. Alizarin with aluminum or calcium salts produces the well-known Turkey red. 

Aromatic natural products of polyketide origin are less prevalent in plants compared with microorganisms. The majority of the plant constituents that contain aromatic stmctures are known to arise from the shikimate pathway (see below). Unlike those derived from the shikimate pathway, aromatic products of the polyketide pathway invariably contain a meta oxygenation pattern because of their origin from the cyclization of polyketides. Phenolic compounds such as chrysophanol-anthrone (Bl), and emodin-anthrone (B2), and the anthraquinones, aloe-emodin (B3) and emodin (B4) (Fig. 2), are products of the polyketide pathway and are found to occur in some plants of the genera Cassia (Leguminosae) (21), Rhamnus (Rhamnaceae) (22), and Aloe (Liliaceae) (23). The dimer of emodin-anthrone (B2), namely hypericin, (B5) is a constituent of the antidepressant herbal supplement, St. John s wort (Hypericumperforatum, Hy-pericaceae) (24). 

In addition to hydroxyanthraquinones such as alizarin, which is derived from shikimate, glutamate and mevalonate precursors, higher plants produce some polyketide anthraquinones identical to those of microbial origin. Of particular interest is the cooccurrence in root extracts of Aloe species of the 2-methylanthraquinone chiysophanol (63) and the isomeric 1-methylanthraquinone aloesaponarin II (64), since in microorganisms 63 has only been isolated fi om fungal species whereas 64 is the product of a recombinant streptomycete (Figure 7). 

Anthranoid laxative plants The anthranoid-containing plants are essentially similar in their mode of action. In this group the active substances are a group of polynuclear or tricyclic hydrocarbon derivatives based on anthracene. Various oxidised and reduced forms constitute the aglycones of a variety of C and O glycosides. The fully oxidised form is the anthraquinone form, with the partially reduced form represented by the an-throne nucleus. Dimeric forms whereby two anthracene nuclei are chemically linked to... 

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