Hyperforin derivatives

Gey, C Kyrylenko, S Hennig, L., Nguyen, L.H., Biittner, A., Pham, H.D. et al. (2007) Phloroglucinol derivatives guttiferone G, aristoforin, and hyperforin inhibitors of human sirtuins SIRTl and SIRT2. Angewandte Chemie, 119, 5311-5314. 

The pharmacological activity of SJW extracts has recently been reviewed (55-58). Recent reports have shown that the antidepressant activity of Hypericum extracts can be attributed to the phloroglucinol derivative hyperforin (59-62), to the naphthodianthrones hypericin and pseudohypericin (18,63-65), and to several flavonoids (66-69). The role and the mechanisms of action of these different compounds are still a matter of debate. But, taking these previous findings together, it is likely that several constituents are responsible for the clinically observed antidepressant efficacy of SJW. 

Single- and multiple-dose pharmacokinetic studies with extracts of SJW were performed in rats and humans, which focused on the determination of plasma levels of the naphthodianthrones hypericin and pseudohypericin and the phloroglucinol derivative hyperforin. Results from pharmacokinetic... 

Another common plant that appears to have some activity against MRSA is Hypericum perforatum L., commonly known as St. John s wort. In traditional folk medicine, oily extracts of St. John s wort are used for topical treatment of wounds, bums and myalgia [39]. The lipophilic phloroglucin-derivative hyperforin. Fig. 3, has antibacterial effects and has been shown to inhibit the growth of MRSA at a concentration of 1 (ig/ml [39]. Thus, investigating known plants based on their historical medical (ethnomedical) use is a potentially useful means of discovering new alternative antimicrobial agents. 

Europe are impressive at 6 billion in 1999, outselling Prozac by a factor of 4. The constituents of St.John s wort include naphthodianthrones such as hypericin (96) and pseudohypericin (97), the phloroglucinol derivative hyperforin (98), and various flavonoids such as quercetin (99), rutin (100), quercitrin (101), and biapigenin. ... 

The drug contains peculiar chemical constituents such as naphtodianthrones (hypericins), acylphloroglucinols (hyperforins), flavonol glycosides (quercetin derivatives) and biflavones [9] and all the metabolites as a whole seem to contribute to its pharmacological activity. Current use of St. John s Wort is mainly for the treatment of mild to moderate depression [10,3] and drug extracts for antidepressant applications have become increasingly popular. 

They resemble hyperforin in their chemical structure, having in addition a 2,2-dimcthyl-2//-pyran ring, most probably derived by the cyclization of a 3-methylbut-2-enyl side chain with an enolic hydroxyl group. Only a few reports describe a similar natural tricyclic system [59-60]. 

Important antimicrobial activity is also described for phloroglucinol derivatives other than hyperforin. Thus, some of the phloroglucinols isolated from H. japonicum [55] have been assayed against Gram-positive bacteria and found to be particularly effective against S. aureus. The presence of a benzoyl group on the filicinic acid moiety, typical of their structure, seems to be essential for their bioactivity. 

Two compounds most likely derived from the same biogenetic pathway as hyperforin 10, hyperevolutin A 19 and B 20 were isolated from an African species, Hypericum revolutum VAHL, by Decosterd et al. [50]. A petroleum ether extract of the root bark of this plant yielded both components as the main biologically active constituents. The structure of... 

Hop bitter acids and hyperforin are both derived from three different building blocks a branched short-chain CoA ester derived from amino acid metabolism and three C units derived from malonyl-CoA constitute the acyl phloroglucinol core, which carries two to several isopentenyl side chains that originate from terpenoid metabolism (Adam et al., 2002 Drawer and Beier, 1976 Goese et al., 1999 Karppinen et al., 2007). 

In addition, units derived from DMAPP are found in natural products of mixed biosynthetic origin, e.g., prenylated flavonoids, hop bitter acids, and hyperforins. 

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