Podolactone

Podolactones are considered to be a group of natural products whose basic skeleton contains a y-lactone between carbons 19-6 and a 6-lactone between carbons 12-14, which are their characteristic functions Fig. (1) [1]. The numbering of the podolactone skeleton has been assigned on the basis of the totarane skeleton from which most of podolactones have been proposed to be derived. 

The podolactones with a nor- or bisnorditerpenoid structure are mainly found in different species of the Podocarpus plant type [2-3]. Apart from... 

Appearance of podolactones in the extracts of Podocarpus species along with various derivatives with a totarane skeleton (totarol, 12-... 

Natural podolactones can be classified into three major structural types depending on the nature of the conjugated lactone system in the B/C ring moiety [21], Fig. (2). 

Below we can see all the podolactones described up to date, distributed according to the aforementioned classification with an indication of the species from which they were identified and their bibliographic reference. First, the podolactones isolated from Podocarpus species are presented and, later, the podolactones found in fungi will be listed. 

BIOLOGICAL ACTIVITY OF PODOLACTONES Anti-tumoral Activity, a) Yoshida Sarcoma. 

The in vitro bioactivitivity of 29 podolactones, 15 of them natural products, against cultured Yoshida Sarcoma cells [64-65] was investigated by Hayashi s group during the period between 1975 and 1979. 

Table 1 summarizes the obtained results. Podolactones were grouped on the basis of the previously reported structural subgroups in which these natural compounds had been classified. 

Table 1. Citotoxicity of natural and synthetic podolactones against Yoshida Sarcoma...

Recently, Barrero et al. [20] have tested the activity of natural podolactones LL-Z1271a (63) and 68, and of synthetic derivatives 94-99, the latter being a mixture of isomers, against four tumoral cell lines P-388, A-549 (human lung carcinome), HT-29 (human colon carcinome) and MEL-28 (human melanome) (Table 2). The two natural compounds, as well as 98 showed a potent activity (ICso[Pg.470]

Very recently, in 1999, an European patent was published involving the description of a pharmaceutical composition, which includes terpenoid dilactones isolated from a new strain of Oidiodendrum griseum filamentous fungi, together with some semi-synthetic derivatives from the isolated natural podolactones [7]. This pharmaceutical composition was reported to be useful for the treatment of IL-1 (interleukin-1) and TNF (tumor necrosis factor)-mediated diseases. 

Tnble 4. Antifungal activity of podolactones alone or in combination with V4 MIC of anethol... 

Podolactone A (29) happened to be the less toxic lactone, and the most active compounds are nagilactone D (4) and podolactone E (51). These podolactones did not produce mortality when applied topically to larvae or adults (5 pg per insect), which suggests that these compounds are not... 

The methanolic extract of the leaves of P. gracilior (Kenya) caused mortality within 12 days after incorporation into a meridic artificial diet of several lepidopterous pest species. The toxic and growth inhibitory action of nagilactones C (3), D (4) and F (55) and podolide (39) towards these species are shown in Table 7. All tested podolactones are relatively potent growth inhibitors (ED50 4-30 ppm), while the concentration of the compounds that cause mortality was about two orders of magnitude... 

The studies on the inhibitory effects of podolactones A (29) and E (51) and nagilactone E (36) were extended to a range of bioassays [73]. In some of these assays, the effects of the podolactones were compared to those of lycoricidinol and harringtonolide, plant growth inhibitors (Table... 

Table 9. Concentration of podolactones and related compounds causing significant (P = 0.05) inhibition...

Reduction of mature spikelets in Lolium temulentum Podolactone A (29) 0.27... 

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