Anti-inflammatory diterpenoids

Fenical, W. (1987) Marine soft corals of the genus Pseudopterogorgia a resource for novel anti-inflammatory diterpenoids. /. Nat. Prod., 50, 1001-1008. 

Look, S.A., Burch, M.T., Fenical, W., Qi-Tai, W., and Clardy, J. (1985) Kallolide A anti-inflammatory diterpenoid and related lactones from Caribbean octocoral Pseudopterogorgia kallos (Bielschowsky). J. Org. Chem., 50, 5741-5746. 

One of the most exiting findings in this area is perhaps the isolation of Bt-CD, a neoclerodane diterpenoid from Baccharis trimera (Less) DC or carqueja (Brazil) used to treat rheumatism and diabetes that shows anti-phospholipase A2 activity (11). Note also the anti-phospholipase A2 and anti-inflammatory activity of Santolina chamaecy-parissus (12). Cirsium japonicum DC, Crossotephium chinense L. Makino, Inula chinensis Rupr. ex Maxim., and Sigesbeckia orientalis L. are used in Asia for the treatment of inflammatory conditions. 

From the marine alga Stypopodium flabelliforme, several diterpenoids with interesting biological properties were isolated. The diterpenoid epitaondiol exhibited a potent anti-inflammatory activity related to inhibition of human PLA2 activity and leukocyte accumulation [64], Additionally, epitaondiol has been shown as a potent calcium antagonist in... 

Tables 2-5 list monoterpenoids (Mo), sesquiterpenoids (Sq), diterpenoids (Di), and retinoids (Re), sesterterpenoids (St), meroterpenoids and miscellaneous terpenoids (Me), respectively, discussed in this review. The bioassay systems in which the compounds exhibited inhibitory effects, together with the major sources of the compounds, are included in the Tables. Most of these terpenoids are isolated from natural sources, and their structures are shown in Figs. (2)-(5). Some terpenoids which exhibit significant and/or a broad range of chemopreventive and anti-inflammatory activities are discussed below.

The range of biological activity that has been recorded for 14-membered-ring diterpenoids is remarkably wide They were found to function as insect trail pheromones, termite allomones, neurotoxins, cytotoxins, and anti-inflammatory and antimitotic agents. 

Pseudopterosin A (129), which is a diterpene glycoside isolated from the sea whip Pseudopterogorgia elisabethae, shows anti-inflammatory activity by inhibiting release of leukotriene B2 from leukocytes (2, 35). A more interesting class of diter-penes includes sarcodictyn A (130) and elentherobin (131), which were isolated from the soft corals Sarcodictyon roseum and Eleutherobia sp., respectively. These diterpenoids show potent cytotoxicity by stabilizing microtnbnles (2, 35). 

Anti-inflammatory activity was studied on two labdane derivatives isolated from S. javalambrensis [122-124], that also contains other known diterpenoids [98,99,125]. These two products, ent-13-epi-12a-acetoxy-manoyloxide (76) and e t-8a-hydroxy-labda-13(16), 14-diene (98) were evaluated for anti-inflammatory action in vitro in the concentration range 10 7 M to 10 4 M and were compared with aspirin, sodium salicylate and indomethacine neither compound affected superoxide generation or scavenging and nor did inhibit non-enzymatic lipid peroxidation. These two natural products interact with the eicosanoid system, perhaps at the phospholipase level, but do not interfere with the other tested leukocyte functions or with reactive oxygen species, and are essentially non-toxic to... 

This biochemical profile distinguishes these diterpenoids from the antiinflammatory polyphenolics, such as flavonoids occurring in the genus Sideritis, and suggests that medicinal decoctions of these plants are likely to owe any anti-inflammatory activity to more than one bioactive ingredient. 

From a taxonomically distinct and still unidentified specie of the Pseudopterogorgia genus, a related series of pseudopterosins containing bicyclic diterpenoid glycosides, 7 seco A-D, were also isolated and their structures elucidated by Look and Fenical [18]. Compounds 7 seco A-D possess potent anti-inflammatory and analgesic activities that are similar to the pseudopterosins, and also show antimicrobial activity towards the bacteria. Staphylococcus aureus. For example 7 seco-A, pseudopterosin exhibited a 69% reduction of inflammation in the mouse ear edema assay at a minimum inhibitory concentration (MIC) of 50 pg/ear. 

The four lactones, kallolides 82-85, isolated from Pseudopterogorgia hallos (Bielschowsky) by Look et al. [54], are closely related to the cembrolide class of compounds and possess the pseudopterane skeleton (i.e. 62). Among these diterpenoids, the major metabolite kallolide 83, displays the same efficacy as the anti-inflammatory inhibitor, indomethacin (see table 1). 

Diterpenoid tanshinones were found exclusively in the genus Salvia and attracted particular attention from many researchers for their wide-ranging pharmacological activities such as antibacterial, antioxidant, anti-inflammatory, and antineoplastic [3]. Tanshinone I (Tan-I) (1), tanshinone IIA (Tan-IIA) (11), and cryptotanshinone (13) are the major constituents of S. miltiorrhiza. A related plant S. columbariae, which has been used by California Indians in the treatment of strokes, also contains tanshinones, especially cryptotanshinone [7, 8]. This chapter will summarize about the structural properties, the activities against a variety of tumors and cardiovascular diseases, and biosynthesis of tanshinones. 

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