Sulfated sterols

Ibisterol sulfate (550) is a sulfated sterol from a deepwater Topsentia sp. that was cytoprotective against HIV-1 in the NCI primary screen [457]. 

The phylum Echinodermata comprises about 7000 living species [177]. Echinoderm means spiny-skinned and these organisms are characterised by the tube feet, which they use to move about. These have suction discs on the ends, which operate by an internal bulb pumping water in and out of the foot, causing expansion and contraction. The phylum is sub-divided into five classes the asteroids (sea stars), the holothurians (sea cucumbers), the crinoids (sea lilies), the echinoids (sea urchins) and the ophiuroids (brittle stars) [178]. As stated in the introduction to this review, sulfated sterols and saponins, which comprise the majority of echinoderm metabolites containing sulfur, are not included here. 

Additionally, sulfated sterols have been described from a wide variety of marine organisms, particularly sponges and echinoderms, and several of these steroidal sulfates have exhibited a broad range of activities. Halistanol sulfates are a group of sulfated polyhydroxysteroids from... 

Unlike other sulfated sterols of marine origin, the AB and carolisterols (42,43) isolated from Styracaster caroli spp. have not shown any protection against the cytopathic effects of HIV-1 in NCI s primary anti-HIV screen (34). 

These sterol sulfate esters show activity in a number of enzyme and receptor-binding assays and are also active in the anti-HIV screen run at the US National Cancer Institute. A dereplication scheme for this class of compounds has been published by Cardellina et al. (36), in which extracts are chromatographed in three systems Sephadex G-25 for molecular weight C4 wide pore (300) and CIS narrow pore (60 A). Fractions are assayed against HIV and the patterns of activity compared to that observed for halistanol sulfate. Sterol sulfates from six sponge extracts were eluted with methanol H20 (2 1 v/v) and allowed for the rapid dereplication of this class of compound. In... 

McKee, T., Cardellina, J. H., Tischler, M., Snader, K. M., Boyd, M. R. (1993) Ibisterol sulfate, a novel HIV-inhibitory sulfated sterol from the deep water sponge Topsentia sp. J. Nat. Prod. 34, 389-392. 

Sulfated sterols Ibisterol trisodium sulfate (280), Halistanol trisodium sulfate (281),26-Methylhalist-anol trisodium sulfate (282), 25-Demethylhalistanol trisodium sulfate (283) Sponge Spp., Topse-nlia, HaUchondria cf. moorei, Pseudaxinyssa digitata HlV-1, HIV-2 Cytotoxicity, HIV-RT [207]... 

Sulfated sterols from brittle star Macrophiotrix longipeda have been isolated by Elyakov et al. (696) who compared the sterol composition of the sulfated compounds with that of the free steroids. The latter were A -, and A -sterols, with cholesterol as the main... 

Elyakov, G.B., S.N. Fedorov, A.D. Chumak, V.V. Isakov, and V.A. Stonik Sulfated Derivatives from Marine Invertebrates - 1. Sulfated Sterols from Some Species of Echinoderms. Comp. Biochem. Physiol. 71B, 325 (1982). 

The first example of a 6a sulfated sterol was isolated from Dysidea Jfagilis from the lagoon of Venice in 1995, and in 1998 a group of ten 4a sulfated sterols, acanthos-terol sulfates A-J, were characterized in a Japanese sponge of the genus Acanthodendrilla (Dendroceratida). Some of these (I and J) are antifungal. 

The Sterol fraction of Gymnocrinus richeri contains 14 derivatives nine usual sulfated sterols (A5 and AO) and some unusual steroids, including 5a-ergosta-7,22-diene-3p,5,6P-triol, cholesta-l,4-diene-3-one and three A6-5a, 8a epidioxysterols (De Riccardis et al., 1991b). 

Figure 26.11 Examples of side chains of 3a-sulfated sterols from ophiuroids.

Sulfated sterols have several types of biological activity, in particular antiviral activily, which has aheady been mentioned in relation to sponges (see Chapter 19). Studies of structure-activity relationships have established that the presence of sulfate groups on rings A and B contributes greatly to this activity, whereas their presence on ring D has no effect. The presence of sulfate groups on the side chain, in particular on carbon 21, induces only little activity... 

McKee et cd., 1994 Comin et al 1999). These results have been confirmed for some sulfated sterols of ophiuroids, such as one that has been isolated from the species Ophioplocus januarii, which is sulfated at 2a and 21 and which has marked activily against four RNA viruses affecting humans herpesvirus type 1 (HSV-1), poliomyelitis virus (PV), respiratory syncytial virus (RSV) and Argentine hemorrhagic fever virus (Jimin virus) (Roccatagliata et al., 1996) (Table 26.6). 

Another interesting activity of sulfated sterols is inhibition of protein tyrosine kinase pp60, which is involved in the prcKess of cell multiphcation and whose inhibitors are potential anticancer agents. This is the case for five derivatives isolated from Ophiarachna incrassata (Fu et al., 1994). 

The main characteristic of sterols and sulfated sterols of sea stars is the preponderance of A7 sterols compared with AS sterols. The three best-known examples are A7 analogs of 24-nor-A22-cholesterol, occelasterol and gorgosterol -asterosterol, amuresterol and acanthasterol, respectively -whose names derive from the species in which they were discovered (stdfated acanthosterols were isolated from the sponge Acanthodendrilla sp. see Chapter 19). Experimental details of these three sterols are given by Schmitz (1978). 

Though the free sterols are mostly A7, the sulfated sterols are A5 or A7, as is the case for Asterias ruhens,... 

Table 26.7 Free and sulfated sterols %) of Asterias rubensf ...

Figure 26.12 Examples of nonglycosylated side chains of 3 3-sulfated sterols of sea stars. (For side chains sc-1 to sc-15, see Figure 26.11.

This organism may have yielded the largest mimher of sterols, since 85 were found in the three free sterol fractions (20 sterols), including two major A9(ll) sulfated sterols (34 sterols) and steroidal sylosides (31 sterols). 

D Auria, M.V., Ricdo, R., Uriarte, E., Minale, L., Tanaka, J., and Higa, T. (1989) Isolation and structure eluddation of seven new polyhydroxylated sulfated sterols from the ophiuroid Ophiolepis superba.J. Org. Chem., 54, 234—239. 

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