Diterpenes cytotoxic

Cytotoxic diterpenes Salvia miltiorrhiza SiOj RP18 Hx - AcOEt MeOH - H2O — Isolation 51 i— L> -< 0)... 

The plant is known to produce norbisabolane diterpenes, including phyllanthusols A and B, which are both cytotoxic (36). From the bark, pentacyclic triterpenoids, phyl-lanthol, and olean-12en-3[3-ol (p-amyrin) have been isolated (37). Note lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus, such as olean-12-en-3 (3,15 a-diol, olean-12-en-3 [3,15 a,24-triol, lupeol, and betulin inhibited the enzymatic activity of topoisomerase II activity with IC50 values in the range of 10 to 39 p.M (38). 

Fig. 6.5 Formulae of the isolated diterpenes from S. hypargeia and from some other Salvia species with cytotoxicity against the A27 0 cell line...

Kohmoto, S. McConnell, O.J. Wright, A. Cross, S. (1987) Isospongiadiol, a cytotoxic and antiviral diterpene from a Caribbean deep water marine sponge, Spongia sp. Chem. Lett., 1687-90. 

The cyanthin diterpenes show physiological activity ranging from cytotoxicity to nerve-growth factor stimulation. Andrew J. Phillips of the University of Colorado recently described (J. Am. Client. Soc. 2005,127,5334) a concise cnantioselective synthesis of cyanthiwigin U 3, based on the metathesis conversion of 1 to 2, using the second generation Grubbs catalyst. 

Various other biologically active diterpenes have been isolated from plants and are used by man for the treatment of a variety of diseases. The bark of Pinus strobus (Pinaceae), rich in diterpenes, among them manoyl oxide, is used in anticough syrups, whilst traditionally it has been used for the treatment of coughs, colds, congestion, injury, rheumatism and swelling by Indian Americans [26], The antiinflammatory and antimicrobial activity of various diterpenes has been reported [27], as well as anti-fungal activity [28] and remarkable cytotoxic activity for some of them [27,29],... 

A variety of biological activities have been associated with labdane diterpenes including antibacterial, antifungal, antiprotozoal, enzyme induction, anti-inflammatory modulation of immune cell functions, as well as cytotoxic and cytostatic effects against human leukemic cell lines. 

In addition to the (antimicrobial, enzyme and endocrine related) properties mentioned above, it is interesting that many labdane type diterpenes also exhibit significant properties against cancer cells. A number of labdane type diterpenes tested exhibited remarkable antiproliferative and cytotoxic activities. Itokawa et al. [193] found that extracts from the rhizomes of Hedychium coronarium (Zingiberacae), cause growth inhibition of Chinese hamster V-79 cells and sarcoma 180 ascites in mice. Chemical analysis led to the isolation of 8 (17), 12 (E)-labdadiene-15, 16-dial along with four new coronarins (A-D). All of the compounds exhibited... 

Iliopoulou D, Mihopoulos N, Vagias C, Papazafiri P, Roussis V (2003) Novel Cytotoxic Brominated Diterpenes from the Red Alga Laurencia obtusa. J Org Chem 68 7667... 

Sheu J-H, Sung P-J, Cheng M-C, Liu H-Y, Fang L-S, Duh C-Y, Chiang MY (1998) Novel Cytotoxic Diterpenes, Excavatolides A-E, Isolated from the Formosan Gordonian Briareum excavation. J Nat Prod 61 602... 

Biard J-F, Malochet-Grivois C, Roussakis C, Cotelle P, Henichart J-P, Debitus C, Verbist J-F (1994) Lissoclimides, Cytotoxic Diterpenes from Lissoclinum voeltzkowi Michaelsen. Nat Prod Lett 4 43... 

Uddin MJ, Kokubo S, Ueda K, Suenaga K, Uemura D (2001) Haterumaimides F-I, Four New Cytotoxic Diterpene Alkaloids from an Ascidian Lissoclinum Species. J Nat Prod 64 1169... 

Fu X, Palomar AJ, Hong EP, Schmitz FJ, Valeriote FA (2004) Cytotoxic Lissoclimide-Type Diterpenes from the Molluscs Pleurobranchus albiguttatus and Pleurobranchus forskalii. J Nat Prod 67 1415... 

The natural product eleutherobin (1) was isolated in 1994 by Fenical et al. from a marine soft coral from an Eleutherobia species and its structure was elucidated shortly afterwards (Figure 1) [1]. Eleutherobin is a diterpene glycoside that possesses remarkable cytotoxicity against a wide variety of cancer cells, which is likely to be based on binding to tubulin and stabilization of microtubules [2, 3]. Mitosis is interrupted and the cell division cycle is terminated. The mechanism of action of eleutherobin is comparable to that of highly potent cytostatic agents such as paclitaxel (Taxol), nonataxel, epothilones, and discodermolide. 

Table 3 Antiviral activity and cytotoxicity of the diterpene alkaloids...

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