Review Article | Open Access
Pharmacological activities of sulphated steroids derived from marine sources
Nick Savidov1, Tatyana A. Gloriozova2 and Valery M. Dembitsky1,3*
Lethbridge, Canada AB T1K 1L6
2Institute of Biomedical Chemistry, Moscow, Russia, 119121
3National Scientific Center of Marine Biology, Vladivostok, Russia, 690041
*Corresponding author: Valery M. Dembitsky
Biochemical Lab National Scientific Center of Marine Biology, 17 Palchevsky Str., Vladivostok, Russia 690041 Tel. (7423) 2310905; Fax: (7423) 2310900, E-mail:email@example.com
Received: June 3rd, 2018; Accepted:June 28th, 2018 ; Published:June 30th, 2018
Life Sci Press. 2018; 2(1): 48-58. doi: 10.28964/LifesciPress-2-107
Ⓒ 2018 Copyright by Dembitsky VM. Creative Commons Attribution 4.0 International License (CC BY 4.0).
This review is devoted to sulphated steroids that are produced by brittle star, starfish, sponges, ascidian, snails and algae. Mono sulphated steroids have the pharmacological potential on anti-hypercholesterolemic, anti-neoplastic, and anti-inflammatory activity estimated with a confidence of 88 to 92 percent. Di-sulphated steroids that produced by marine starfish are predicted as having anti-neoplastic, anti-inflammatory and anti-hypercholesterolemic activity with a confidence of 78 to 89 percent. In addition, they may have potential immunosuppressant and hepatoprotective inhibitors estimated with a confidence of 73 to 83 percent. Tri-sulphated steroids exhibit anti-inflammatory and antineoplastic activities with a confidence level of 74 to 82 percent.
KEYWORDS: Steroids, lipids, sulphated, marine sponges, starfish, anticancer.
Sulphated compounds, including steroids are widely distributed in nature.1-8 Sulphated steroids are found in many animals, reptiles and humans.9-12 In addition, they are present in extracts of plants and some shrubs, are produced by fungi, and also found in many marine invertebrates such as brittle star, starfish, sponges, ascidian, snails and algae.1,13-15
One of the known and studied functions of sulphated steroids is that they are like a storehouse of biologically active steroid hormones.16 As is known, sulphated steroids are biologically inactive molecules in cells and acquire activity under the action of steroid sulfatase (STS) enzyme, which removes the sulphate group in steroids.16-21 STS inhibitors are potential therapeutic drugs for the treatment of steroid-dependent cancers such as breast, prostate, endometrial cancer, as well as melanoma cells SK-MEL-28, SK-MEL-5 and RPMI-7951.18,22-26 Recently, various groups of scientists have shown that sulfonated steroids can perform the functions of endogenous neuromodulators.27-29
Relationships between chemical structure and biological activity have been known for over 150 years.30 This principle is widely used in pharmacology, biochemistry, bioorganic chemistry and medicine. There are different approaches and methods, but the relationships between structure and activity are constantly preserved. As one of the existing methods is the computer program PASS, which contains about one million chemical compounds and more than 8,000 biological activities. In a number of publications, this method was used and it proved to be very practical with a large degree of effectiveness.31-34 The algorithm of PASS practical utilization is described in detail in several publications.35-39
This review is devoted to sulphated steroid derived from marine sources and their confirmed and predicted biological activities.
Steroid Mono sulphates
Currently, more than 150 sulphated steroids have been found in marine invertebrates and algae. We selected about a third of the steroids that are of potential interest for practical and clinical medicine. 1,15
Cholesterol sulphate (1, structure see Figure 1 and activities see Table 1) has been isolated from the starfish, Asterias rubens.40,41 Cholesterol sulphate (1) and cholestanol sulphate (2) and were identified as the major components among the 34 different sterol sulphates of the sea cucumber Eupentacta fraudatrix.42
The 24-methylidene-cholesterol sulphate (3) was found in the diatomic microalga Nitzchia alba more than 50 years ago,43 and other derivative of cholesterol sulfate called hymenosulfate (4) with an unusual side chain was found in the haptophytic microalga Hymenomonas sp.44 Three sulphated sterols, cholesterol sulphate (1), 24-methylcholest-5-en-3β ol sulphate (5) and 5- sitosten-3β-ol sulphate (6) produced by the diatom Skeletonema marinoi.45 The cholest-5-ene-3β-sulfate sodium (7) was isolated from the methanol extract of the sea urchin Diadema savignyi.46
Two derivatives of cholesterol sulphate (8 and 9) were isolated from the tropical marine cucumber Holothuria sp.,47 and two derivatives of cholestanol sulphate (10 and 11), and minor sterols (12-16) were detected in the Far Eastern holothurian Eupentacta fraudatrix.42
An Australian marine sponge Stilopus australis produced sulphated steroid with the pregnane skeleton (17).48 An annasterol sulphate (18) was isolated from the Pacific deep-water sponge Poecilastra laminaris, and this compound showed a β-1,3-glucanase inhibitor.49 Polyhydroxysteroid monosulphate (19) was found in extract of the sponge Toxadocia zumi.50 Rare steroid monosulphate with the sulfate group in 2β-position (20) was isolated from sponge Echinoclathria suhispida collected from the Japan Sea near the coast of Japan.51 The Malaysian sponge Haliclona sp. from an Indo-Pacific has yielded haliclostanone sulphate (21).52 The unique cytotoxic steroid (22) containing a sulphate group in 6α-position was found in the sponge Dysidea fragilis collected from the lagoon of Venice, Italy.53 Sulphated steroid called apheloketotriol (23) was isolated from a Far Eastern sponge Aphelasterias japonica,54 and acanthosterol E (24) was found in the sponge Acanthodendrilla sp. contain sulphate group in 6-position.55
Rare monosulphate (25) containing sulfate group in 16-position was found in starfish Luidia clathrata (family Luidiidae)56 although the other 3-monosulfate (26) was isolated from Far Eastern starfish Luidia quinaria (Japan Sea).57
Three sulfated steroidal glycosides (27-29, structure see Figure 2 and activities see Table 2) were isolated from the visceral extract of the cone snail Conus pulicarius. The three new compounds exhibited significant in vitro cytotoxicity (GI50 values down to 0.49 µM) against the K562 human leukemia cell line.58
Three sulfated steroid monoglycosides, leptaochotensosides A–C (30–32), and a sulphated polyhydroxylated steroid (33) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis.59 Leptaochotensoside A (30) demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of (30) is realized through regulation of mitogen-activated protein kinase (MAPK) signaling pathway.
A rare sulphated steroid at position 5, named phallusiasterol A (34) was isolated from the Mediterranean ascidian Phallusia fumigate.60 Polyhydroxylated sterol called asterosaponin P2 (35), with the sulfate group only in the side chain, isolated from the Far-Eastern starfish Patiria (Asterina) pectinifera,61 exhibited activity against HSV-1, with MIC values of 0.07 μM.62
A series of sulphated steroid-containing amide fragment (36-41) were isolated from marine invertebrates. So starfish, Styracaster caroli which was collected at a depth of 2000 m between the islands of Thio and Lifou (New Caledonia) contained unique polyhydroxylated steroids in water-acetone extract (36 and 37).63 The same steroids (36-39 and 41) were found in the sponge Polymastia boletiformis.64,65
Sulphated steroid xyloside, minutosides B (40) has been isolated from the brine shrimp active fraction of the ethanolic extract of the starfish Anasterias minuta. This xyloside exhibited antifungal activity against Cladosporium cucumerinum and Aspergillus flavus.66
Di- and tri-sulphate steroids
Di- and trisulphates of steroids represent a fairly rare group of lipids. Their total content in marine organisms is two to three times less than that of steroids containing one sulphate group.1,15 Тhe antiviral orthoesterol B (42, structure see Figure 3 and activities see Table 3) showed antiviral activity was found in the marine sponge Petrosia weinbergi.67 Weinbersterol B (43), sulphated tetrahydroxy steroid with an unprecedented cyclopropane-containing side chain, was isolated from the sponge Petrosia weinbergi. This compound is active in vitro against feline leukemia virus, and active in vitro against HIV.68
A series of steroid disulphates were found in starfishes and ophiuroids. Thus compound (44) was isolated from the starfish Tremaster novaecaledonia63 and from Aphelasterias japonica.69
Brittle stars are echinoderms and belong to the class Ophiuroidea produce a large number of active metabolites including lipids, fatty acids and steroids.70-74 Sulphated stanols are widely distributed in various representatives in more than 30 species of Ophiuroidea.1,13 Disulphate stanol (45) was first discovered in brittle star Ophioderma longicaudum 75 and another steroid (46) containing an additional hydroxy group at C12 was isolated from the ophiuroids Ophioderma longicaudum from the Mediterranean Sea.1,15,76 The disulphated steroid (47) containing three functional groups in the ring A was isolated from the antarctic brittle star Ophiosparte gigas,77 the same steroid also was found in Astroclades exiguus and Amphiophiura ponderosa.78 Rare sulphated steroid (49) containing sulphate groups in 2β- and 21α-positions, was detected in extracts from the starfishes of the starfish Pteraster tesselatus.79
Trisulfated polyhydroxysteroids are rare and typical metabolites which produced by marine sponges and echinoderms.1,15,80 Halistanol sulphate sodium (50), the most widespread sponge steroid sulphate, was discovered from the sponge Halichondria moori by Fusetani and co-workers more than 35 years ago.81 Analogue of compound (50), halistanol sulfate I sodium (51) was isolated from a marine sponge Halichondria sp. collected at Hachijo-jima Island. Obtained steroid showed inhibitory activity against SIRT 1-3 with IC50 of 45.9, 18.9 and 21.8 μM respectively.82
Polyhydroxylated sterol derivatives called topsensterol B (52) has been isolated from a marine sponge Topsentia sp. collected from the South China Sea. Isolated compound exhibited cytotoxicity against human gastric carcinoma cell line SGC-7901 with an IC50 value of 8.0 μM,83 and topsentiasterol sulphate E (53) was found in the sponge Spheciospongia sp., collected in the Philippines. This compound inhibited PKCzeta with IC50 value of 1.21 µM, and in a cell-based assay, also inhibited NF-kappa B activation with EC50 value of 12 µM. 84
Representatives of ophiuroids contain very interesting lipid molecules, such plasmalogenous polar lipids and fatty aldehydes.72 In addition, two trisulphated steroids have also been found in various types of ophiuroids, so the steroid (54) is isolated from Ophiura sarsi, and another steroid (57) is isolated from Ophiorachna incrassate.85
Socotrasterol sulphate (58) was isolated from different sponge species86 and ophirapsterol sulphate (55) was found in Topsentia ophiraphidites.87 Rare sulphated sterol dimers called fibrosterol sulphates A (55) and B (56) were isolated from a Lissodendoryx (Acanthodoryx) fibrosa sponge from Coron Island Palawan, Philippines.84 Both compounds have inhibited PKC ζ with IC50 values of 16.4 and 5.6 μM, respectively.88
The sulphated steroids found in the lipid extracts of various marine organisms are an interesting group of biologically active metabolites. As shown by numerous studies in recent years, many of these compounds show anti-cancer and antiviral properties. The data in this review show that sulphated steroids can be used as potential drugs for pre-clinical use and have good chances in the future for use in cancer patients.
This study was not funded, this is a review article.
CONFLICT OF INTEREST DISCLOSURES
All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
The work was performed in the framework of the Program for Basic Research of State Russian Academies of Sciences for 2013-2020.
1. Kornprobst JM, Sallenave C, Barnathan G. Sulfated compounds from marine organisms. Comp Biochem Physiol B Biochem Mol Biol. 1998; 119(1):1-51.
2. Cunha L, Grenha A. Sulfated seaweed polysaccharides as multifunctional materials in drug delivery applications. Mar Drugs. 2016; 14(3). pii: E42. doi: 10.3390/md14030042
3. Da Silva MC, Sousa E, Pinto MMM. Emerging sulfated flavonoids and other polyphenols as drugs: Nature as an inspiration. Med. Res. Revs. 2014; 34(2): 223-279.
4. Dembitsky VM. Chemistry and biodiversity of the biologically active natural glycosides. Chem Biodiver. 2004; 1(5): 673-781.
5. Mougous JD, Green RE, Williams SJ, et al. Sulfotransferases and sulfatases in mycobacteria. Chem Biol. 2002; 9(7):767-776.
6. Almeida JR, Da-Silva MC, Sousa E, et al. Antifouling potential of Nature-inspired sulfated compounds. Sci Rep. 2017; 7, 42424; doi: 10.1038/srep42424.
7. El Bouzidi L, Mahiou-Leddet V, Bun SS, et al. Cytotoxic withanolides from the leaves of Moroccan Withania frutescens. Pharm Biol. 2013; 51(8):1040-6.
8. Teles YCF, Sallett M, Souza R, et al. Sulphated flavonoids: biosynthesis, structures, and biological activities. Molecules 2018; 23: 480-488.
9. Suchański J, Ugorski M. The biological role of sulfatides. Postepy Hig Med Dosw (Online). 2016; 70:489-504.
10. Mensah-Nyagan AG, Beaujean D, Do-Rego JL, et al. In vivo evidence for the production of sulfated steroids in the frog brain. Comp Biochem Physiol B Biochem Mol Biol. 2000; 126(2):213-219.
11. Pauli GF, Friesen JB, Gödecke T, et al. Occurrence of progesterone and related animal steroids in two higher plants. J Nat Prod. 2010; 73(3):338-345.
12. Mueller JW, Gilligan LC, Idkowiak J, et al. The regulation of steroid action by sulfation and desulfation. Endocr Rev. 2015; 36(5):526-563.
13. D’Auria MV, Minale L, Riccio R. Polyoxygenated steroids of marine origin. Chem Rev. 1993; 93(5): 1839–1895.
14. Dembitsky V.M., Paradigm shifts in fungal secondary metabolite research: Unusual fatty acids incorporated into fungal peptides. Int J Current Res Biosci Plant Biol. 2017; 4(12): 7-29.
15. Carvalhal F, Correia-da-Silva M, Sousa ME, et al. Sources and Biological Activities of Marine Sulfated Steroids. J Mol Endocrinol. 2018; pii: JME-17-0252. doi: 10.1530/JME-17-0252.
16. Geyer J, Bakhaus K, Bernhardt R, et al. The role of sulfated steroid hormones in reproductive processes. J Steroid Biochem Mol Biol. 2017; 172:207-221.
17. Hobkirk R. Steroid sulfation: Current concepts. Trends Endocrinol Metabol. 1993; 4(2): 69-74.
18. Shah R, Singh J, Singh D, Jaggi AS, Singh N. Sulfatase inhibitors for recidivist breast cancer treatment: A chemical review. Eur J Med Chem. 2016; 114:170-190.
19. Williams SJ. Sulfatase inhibitors: a patent review. Expert Opin Ther Pat. 2013 Jan;23(1):79-98.
20. Woo LW, Purohit A, Potter BV. Development of steroid sulfatase inhibitors. Mol Cell Endocrinol. 2011; 340(2):175-185.
21. Maltais R, Poirier D. Steroid sulfatase inhibitors: A review covering the promising 2000–2010 decade. Steroids 2011; 76(10–11): 929-948.
22. Foster PA. Steroid metabolism in breast cancer. Minerva Endocrinol. 2008 Mar;33(1):27-37.
23. Foster PA, Reed MJ, Purohit A. Recent developments of steroid sulfatase inhibitors as anti-cancer agents. Anticancer Agents Med Chem. 2008 Oct;8(7):732-8.
24. Day JM, Purohit A, Tutill HJ, et al. The development of steroid sulfatase inhibitors for hormone-dependent cancer therapy. Ann N Y Acad Sci. 2009; 1155:80-87.
25. Levina ÉV, Kalinovskiĭ AI, Ermakova SP, Dmitrenok PS. Steroidal compounds from the Pacific starfish Mithrodia clavigera and their toxic properties against human melanoma cells. Bioorg Khim. 2012; 38(5):591-596.
26. Roccatagliata AJ, Marta S. Maier, Seldes AM, et al. Antiviral Sulfated Steroids from the Ophiuroid Ophioplocus januarii. J Nat Prod. 1996; 59(9): 887–889.
27. Gibbs TT, Russek SJ, Farb DH. Sulfated steroids as endogenous neuromodulators. Pharm Biochem Behavior 2006; 84(4): 555-567.
28. Harteneck C. Pregnenolone sulfate: from steroid metabolite to TRP channel ligand. Molecules. 2013; 18(10):12012-12028.
29. Carta MG, Bhat KM, Preti A. GABAergic neuroactive steroids: a new frontier in bipolar disorders? Behav Brain Funct. 2012; 8:61. doi: 10.1186/1744-9081-8-61.
30. Barlow RB. Structure-activity relationships. Trends Pharm Sci. (1979-1980); 1(1): 109-111.
31. Dembitsky VM, Gloriozova TA. Naturally occurring boron containing compounds: Structures and biological activities. J Nat Prod Resources. 2017; 3(2): 147-152.
32. Gloriozova TA, Dembitsky VM. The impact factor of the thiirane group in organic compounds on their predicted pharmacological activities. Int J Chem Studies. 2018; 6(1): 832-839.
33. Levitsky DO, Gloriozova TA, Poroikov VV, et al. Anabolic cyanosteroids and their biological activities – A brief review. World J Pharm Pharmaceut Sci. 2017: 6(12): 127-151.
34. Kilimnik A, Gloriozova TA, Dembitsky VM. Halogenated (F, Cl, Br, I) Anabolic steroids and their biological activities. Int J Current Res Biosci Plant Biol. 2017; 4(12): 68-93.
35. Sergeiko A, Poroikov VV, Hanus LO, et al. Cyclobutane-containing alkaloids: origin, synthesis, and biological activities. Open Med Chem J. 2008; 2: 26-37.
36. Dembitsky VM, Gloriozova TA, Poroikov VV. Natural steroids containing a tertiary butyl group and their biological activities. Eur J Biomed Pharm Sci. 2017; 4(11): 32-58.
37. Dembitsky VM, Savidov N, Poroikov VV, et al. Naturally occurring aromatic steroids and their biological activities. Applied Microbiol Biotechnol. 2018; 102(11): 4663–4674.
38. Bezhentsev VM, Druzhilovskiy DS, Ivanov SM, et al. Web resources for discovery and development of new medicines, Pharm Chem J. 2017; 51(2): 91–99.
39. Filimonov DA, Lagunin AA, Gloriozova TA, et al. Prediction of the biological activity spectra of organic compounds using the PASS online web resource, Chem. Heterocycl. Comp. 2014; 50(3): 444-457.
40. Björkman LR, Karlsson KA, Pascher I, Samuelsson BE. The identification of large amounts of cerebroside and cholesterol sulfate in the sea star, Asterias rubens. Biochim Biophys Acta 1972; 270(2): 260-265.
41. Björkman LR, Karlsson KA, Nilsson K. On the existence of cerebroside and cholesterol sulfate in tissues of the sea star, Asterias rubens. Comp Biochem Physiol. 1972; 43(2)B: 1972b, 409-410.
42. Makarieva TN, Stonik VA, Kapustina II, et al. Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix. Steroids 1993; 58(11): 508-517.
43. Kates M, Volcani BE. Lipids of diatoms. Biochem Biophys Acta 1966; 116: 264-272.
44. Kobayashi M, Ishibashi M, Nakamura H, et al. Hymenosulphate, a novel sterol sulphate with Ca-releasing activity from the cultured marine haptophyte Hymenomonas sp. J Chem Soc. Perkin Trans 1989; 1: 101-103.
45. Gallo C, d’Ippolito G, Nuzzo G, Sardo A, Fontana A. Autoinhibitory sterol sulfates mediate programmed cell death in a bloom-forming marine diatom. Nat Commun. 2017; 8: 1292-1301.
46. Thao NP, Luyen BT, Kim EJ, et al. Steroidal constituents from the edible sea urchin Diadema savignyi Michelin induce apoptosis in human cancer cells. J Med Food. 2015; 18(1):45-53.
47. Anjaneyulu ASR, Venugopal MJRV, Minale L, Iorizzi M, Pelagiano E. Chemical examination of a sea cucumber of Holothuria genus of the Indian Ocean. Indian J Chem. 1998; 37B: 262-268.
48. Prinsep MR, Blunt JW, Munro MHG. A new sterol sulfate from the marine sponge Stylopus australis. J Nat Prod. 1989; 52(3): 657–659.
49. Makarieva TN, Stonik VA, D’yachuk OG, A S Dmitrenok AS. Annasterol sulfate, a novel marine sulfated steroid, inhibitor of glucanase activity from the deep water sponge Poecillastra laminaris. Tetrahedron Lett. 1995; 36: 129-134.
50. Nakatsu T, Walker RP, Thompson JE, Faulkner DJ. Biologically-active sterol sulfates from the marine sponge Toxadocia zumi. Experientia 1983; 39: 759-761.
51. Li HY, Matsunaga S, Fusetani N, Fujiki H, et al.Echinoclasterol sulfate phenethylammonium salt, a unique steroid sulfate from the marine sponge, Echinoclathria subhispida. Tetrahedron Lett. 1993; 34: 5733-5736.
52. Sperry S, Crews P. Haliclostanone sulfate and halistanol sulfate from an Indo-Pacific Haliclona sponge. J Nat Prod. 1997; 60(1): 29–32.
53. Aiello A, Fattorusso E, Menna M, et al. New cytotoxic steroids from the marine sponge Dysidea fragilis coming from the lagoon of Venice. Steroids 1995; 60: 666-673.
54. Ivanchina NV, Kicha AA, Kalinovsky AI, et al. Hemolytic polar steroidal constituents of the starfish Aphelasterias japonica. J Nat Prod. 2000; 63: 1178-1182.
55. Tsukamoto S, Matsunaga S, Fusetani N, van Soest RWM. Acanthosterol sulfates A−J: ten new antifungal steroidal sulfates from a marine songe Acanthodendrilla sp. J Nat Prod. 1998; 61: 1374-1378.
56. Iorizzi M, Bryan P, McClintock J, et al. Chemical and biological investigation of the polar constituents of the starfish Luidia clathrata, collected in the Gulf of Mexico. J Nat Prod. 1995; 58: 653-658.
57. Andriyaschenko PV, Levina EV, Kalinovsky AI. Chemistry of natural compounds and bioorganic chemistry: Steroid compounds from the Pacific starfishes Luidia quinaria and Distolasterias elegans. Izv. Akad. Nauk, Ser. Khim. 1996; 3: 473-481.
58. Lee YJ, Han S, Kim SH, et al. Three New Cytotoxic Steroidal Glycosides Isolated from Conus pulicarius Collected in Kosrae, Micronesia. Mar Drugs 2017; 15: 379; doi:10.3390/md15120379.
59. Malyarenko TV, Malyarenko-Vishchuk OS, Ivanchina NV, et al. Four new sulfated polar steroids from the Far Eastern starfish Leptasterias ochotensis: Structures and activities. Mar Drugs. 2015 Jul; 13(7): 4418–4435.
60. Imperatore C, D’Aniello F, Aiello A, et al. Phallusiasterols A and B: Two new sulfated sterols from the Mediterranean tunicate Phallusia fumigata and their effects as modulators of the PXR receptor. Mar Drugs 2014; 12: 2066–2078.
61. Kicha AA, Ivanchina NV, Kalinovsky AI, et al. Asterosaponin P2 857 from the Far-Eastern starfish patiria (asterina) pectinifera. Russ Chem Bull. 2000; 49: 1794-1795.
62. Peng Y, Zheng J, Huang R, Wang Y, Xu T, et al. Polyhydroxy steroids and saponins from China sea starfish Asterina pectinifera and their biological activities. Chem Pharm Bull. 2010; 58: 856-858.
63. De Riccardis F, Minale L, Riccio R, et al. A novel group of polyhydroxycholanic acid derivatives from the deep water starfish Styracaster caroli. Tetrahedron Lett. 1993; 34: 4381-4384.
64. Kong F, Andersen RJ. Polymastiamide A, a novel steroid/amino acid conjugate isolated from the Norwegian marine sponge Polymastia boletiformis (Lamarck, 1815). J Org Chem. 1993; 58: 6924-6928.
65. Kong F, Andersen RJ. Polymastiamides B−F, Novel Steroid/Amino Acid Conjugates Isolated from the Norwegian Marine Sponge Polymastia boletiformis. J Nat Prod. 1996; 59: 379-385.
66. Chludil HD, Maier MS. Minutosides A and B, antifungal sulfated steroid xylosides from the patagonian starfish Anasterias minuta. J Nat Prod. 2005; 68(8):1279-1283.
67. Koehn FE, Gunasekera M, Cross SS. New antiviral sterol disulfate ortho esters from the marine sponge Petrosia weinbergi. J Org Chem. 1991; 56(3): 1322–1325.
68. Sun HH, Gross SS, Gunaseker M, Koehn FE. Weinbersterol disulfates A and B, antiviral steroid sulfates from the sponge petrosia weinbergi. Tetrahedron 1991; 47(7): 1185-1190.
69. Finamore E, Zollo F, Minale L, Yasumoto T. Starfish saponins, part 47. Steroidal glycoside sulfates and polyhydroxysteroids from Aphelasterias japonica. J Nat Prod. 1992; 55: 767-771.
70. Dembitsky VM. Betaine ether-linked glycerolipids: chemistry and biology. Prog Lipid Res. 1996; 35(1): 1-51.
71. Dembitsky VM, Srebnik M. Natural halogenated fatty acids: their analogues and derivatives. Prog Lipid Res. 2002; 41(4): 315-367.
72. Dembitsky VM. Lipids of marine origin. A study of Ophiura sarsi phospholipids, Bioorg Chem. (USSR) 1980; 6: 426-429.
73. Dembitsky VM. Plasmalogens in phospholipids of marine invertebrates. Biologiya Morya (Vladivostok) 1979; 5: 86–90.
74. Sato D, Ando Y, Tsujimoto R. et al. Identification of novel nonmethylene-interrupted fatty acids, 7E,13E-20∶2, 7E,13E,17Z-20∶3, 9E,15E,19Z-22∶3, and 4Z,9E,15E,19Z-22∶4, in ophiuroidea (Brittle star) lipids. Lipids (2001) 36: 1371, doi.org/10.1007/s11745-001-0854-x.
75. Shubina LK, Fedorov SN, Levina EV, et al. Comparative study on polyhydroxylated steroids from echinoderms. Comp Biochem Physiol. 1998; 119B: 505-516.
76. Voogt PA. Biosynthesis and composition of 3 -sterols in the ophiuroids Ophiura albida and Ophioderma longicauda. Comp Biochem Physiol B. 1973; 45(313):593-601.
77. D’Auria MV, Paloma LG, Minale L, et al. Isolation and Structure Characterization of Two Novel Bioactive Sulphated Polyhydroxysteroids from the Antarctic Ophiuroid Ophioderma longicaudum. Nat Prod Lett. 1993; 3: 197-208.
78. Comin MJ, Maier MS, Roccatagliata AJ, et al. Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs. Steroids 1999; 64: 335-340.
79. Levina EV, Andriyaschenko PV, Kalinovsky AI, et al. New Ophiuroid-Type Steroids from the Starfish Pteraster tesselatus. J Nat Prod. 1998; 61: 1423-1429.
80. Stonik VA. Marine polar steroids. Russ Chem Rev. 2001; 70(8): 673-715.
81. Fusetani N, Matsunaga S, Konosu S. Bioactive marine metabolites II. Halistanol sulfate, an antimicrobial novel steroid sulfate from the marine sponge Halichondria cf. moorei bergquist. Tetrahedron Lett. 1981; 22: 1985-1991.
82. Nakamura F, Kudo N, Tomachi Y, et al. Halistanol sulfates I and J, new SIRT1–3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria. J Antibiot. 2018; 71(2): 273-278.
83. Chen M, Wu XD, Zhao Q, Wang CY. Topsensterols A–C, Cytotoxic Polyhydroxylated Sterol Derivatives from a Marine Sponge Topsentia sp. Mar Drugs. 2016; 14(8): 146-154.
84. Whitson EL, Bugni TS, Chockalingam PS, et al. Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp. J Nat Prod. 2008; 71(7): 1213-1217.
85. Stonik VA, Ivanchina NV, Kicha AA. New polar steroids from starfish. Nat Prod Commun.2008; 3(10): 158-172.
86. Makarieva TN, Shubina LK, Kalinovsky AI, et al. Steroids in porifera. II. Steroid derivatives from two sponges of the family . Sokotrasterol sulfate,a marine steroid with a new pattern of side chain alkylation. Steroids 1983; 42: 267-271.
87. Gunasekera SP, Sennett SH, Kelly-Borges M. Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites. J. Nat. Prod. 1994; 57: 1751-1754.
88. Whitson EL, Bugni TS, Prdiya S, Chockalingam PS, et al. Fibrosterol sulfates from the Philippine sponge Lissodendoryx (Acanthodoryx) fibrosa: sterol dimers that inhibit PKC ζ. J Org Chem 2009; 74: 5902-5908.