Diarylheptanoids activity

Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa U. (1992). Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm Bull (Tol o). 40(2) 387-91. Kobayashi M, Shqji N, Ohizumi Y. (1987). Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. Biochim Biophys Acta. 903(1) 96-102. 

Prasain, J.K. et al.. Inhibitory effect of diarylheptanoids on nitric oxide production in activated murine macrophages, Biol. Pharm. Bull, 21, 371, 1998. 

Synthetic effort is going on toward the unique diarylheptanoid blepharocalyxin D, 38, which has shown considerable in vitro antiproliferative activity against human fibrosarcoma HT-1080 cells, although this postulated stmcture for blepharocalyxin D is yet to be confirmed by synthesis <2003TL6351>. 

Claeson, P., Panthong, A., Tuchinda, P., Reutrakul, V., Kanjanapothi, D. and Taylor, W.C. (1993) Three non-phenolic diarylheptanoids with anti-inflammatory activity from Curcuma xanthorrhiza. Planta Medica 59, 451-454. 

Claeson, P., Pongprayoon, U., Sematong, T., Tuchinda, P., Reutrakul, V. and Soontornsaratune, P. (1996) Non-phenolic linear diarylheptanoids from Curcuma xanthorrhiza a novel type of topical anti-inflammatory agents structure activity relationship. Planta Medica 62, 236-240. 

Flynn, D.L., Rafferty, M.F., and Doctor, A.M., Inhibition of 5-hydroxyeicosatet-raenoic acid (5-HETE) formation in intact human neutrophils by naturally occurring diarylheptanoids Inhibitory activities of curcuminoids and yakuchinones, Leukot-rienes Med., 22, 357, 1986. 

The major pigment in Curcuma species (Zingiberaceae family) is the yellow phenolic diarylheptanoid curcumin (Jl). Curcumin and its analogs have potent antioxidant and antiinflammatory effects, cytotoxicity against tumor cells, and antitumor-promoting activity (96). The biologic effects and targets of curcumin, as well as its possible roles in cancer prevention and therapy, have been reviewed recently (97, 98). 

Ohtsu H, Itokawa H, Su CY, Shih C, Chiang T, Chang E, Lee YF, Chiu SY, Chang C, Lee KH. Antitumor agents 222. Synthesis and anti-androgen activity of new diarylheptanoids. Bioorg. Med. Chem. 2003 11 5083-5090. 

Other active diarylheptanoids found in nature were the five obtained from the stems of Pinus flexilis (Pinaceae). They have no unsaturations in the linear chmn, except hirsutenone (23), and were potent inhibitors of recombinant human PKCa, with IC50 values ranging from 1.4 to 8.6 pM [76]. 

The constitution of this relatively simple and broadly used compound was established surprisingly late by Lampe and Milobedzka (2), first in 1910 by degradation followed in 1913 by a synthesis (3,4). Curcumin remained the only representative of the group as long as until 1964. In the following 30 years, however, about 70 linear and 35 macrocylic diarylheptanoids were isolated. In the present review we are dicussing their chemistry, phytochemistry, biosynthesis, biological activity, and synthesis. 

Two optically active compounds (5 and 6), for which the fancy names yashabushiketol and dihydro-yashabushiketol were coined, were isolated by Asakawa et al. from A. firma (7,8) and A. sieboldiana species (9), while from the former source Urarova and her coworkers isolated a levorotatoiy saturated diol 7 (10). Absolute configuration of (-)-7 was established to be S,S by Asakawa et al. (11) by correlation with (. 6. In A. firma Suga et al. discovered a dienone (8) (12) which could not be derived from diarylheptanoids isolated earlier. 

Oregonin, an optically active ketol [(. -11) is the diarylheptanoid component of several Alnus species and was first isolated as its xyloside in 1974 from A. rubra (14), but the absolute configuration of the aglycon remained unknown until it was also isolated from A. 

From Alnus species i.e. varieties of alder, containing also a large variety of open chain diarylheptanoids (7-21), some biaryl type macrocyclic compounds have also been isolated. In Alnus japonica Steud. indigeneous in Japan Nomura et al. found four diphenols of this kind. The constitution of alnuson (80) and alnusoxide (81) was elucidated in 1975 (20), while alnusdiol (82) and its oxidation product, alnusonol (83) were characterized in 1981 (17). It was observed that 81 could only be isolated from the dried plant and may be therefore an artefact. Alnusdiol was optically active and therefore a trans-diol but its absolute configuration remained unknown. 

Macrocyclic diarylheptanoids can be derived from linear ones by oxidative cyclization. This is supported by the fact that in all of the biaryl type representatives the aryl-aryl bond is in meta position relative to both ends of the seven-carbon chain, while in those containing a diarylether bond a meta,para bridging can be identified. This substitution pattern corresponds to activation of the position ortho to the phenolic hydroxy group. Biosynthesis of cyclic diarylheptanoids was investigated by Inoue et al. (84). They fed [1- C] and... 

Inhibition of PG biosynthesis by open chain diarylheptanoids was first reported by Itokawa and his coworkers (26, 31). Their results were implemented by studies on additional compounds first by Flynn (88) and later by Kinchi et al. (85). The latter group extended the assay of inhibitor activity also to the 5-lipoxygenase enzyme system. Their results are summarized in Table 2. Among macrocyclic diarylheptanoids only for garuganins (88-95), isolated from Garuga pinnata was some antiinflammatory activity claimed, but no specific data were disclosed (57, 58). 

The inhibition of arachidonic acid metabolism by diarylheptanoids can be attributed to their antioxidant properties. Studies on structure-activity relationships demonstrated that hydroxyl groups were responsible for the antioxidant activity, while an unsubstituted phenyl... 

The only diarylheptanoid showing antibacterial activity so far is centrolobin (68), as reported by Goncalves and his coworkers (99). An interesting observation is that on intensive irradiation by light curcumin (1) became highly phototoxic against Salmonella typhimurium and Escherichia coli (100). 

Among cyclic diarylheptanoids garuganins and garugamblins isolated from Garuga pinnata and G. gamblei (88-95) exhibited antibacterial activity (57, 58). Activity and mechanism of action of the pure isolated constituents is unknown. 

In addition to curcumin, many other constituents in the Zingiberaceae family possess anti-inflammatory activity [15]. Some of these constituents, such as yakuchinones A and B isolated from Alpinia oxyphylla Miquel [16], Fig. (6), are diarylheptanoids and structurally similar to curcumin. 

The first review of diarylheptanoids covered die literature up to October 1993, and a total of 117 substances were listed [1]. Another review on diarylheptanoids, particularly informative on synthetic aspects, subsequently appeared [2]. In the present review, covering reports appearing in major journals during October 1993 - September 1999, information on 114 diarylheptanoids has been found. Out of these, 75 substances are new natural products and for the remaining 39 known compounds, studies on biological activities, re-isolation from other plant sources, synthesis, structure revision etc., have been published. Tables 1-5 list the diarylheptanoids with trivial names, occurrence in nature and pertinent... 

No biological activities have been reported for any Type in diarylheptanoids. 

No studies on biological effects of Type IV diarylheptanoids have been reported, but antibacterial activities of the garuganins from Garuga species have been predicted based molecular mechanics and molecular orbital calculations [47]. 

As seen in the sections above, several of the diarylheptanoids of Types I, n, and V have been reported to exhibit various types of biological activities. Most of these studies have been performed on biomedically relevant targets in vitro (e.g. protein kinase C [14], LPS-activated macrophages [22], CC14-challenged hepatocytes [10], but in vivo anti-inflammatory effects have also been demonstrated for some compounds [3, 17]. Toxic effects on parasites, such as nematodes [6,27] and trypanosomatids [8] have also been recorded for the first time. 

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