Pounina TA , Gloriozova TA , Savidov N , Dembitsky VM .

	Figure 1. Mono sulfated steroids are derived from marine sources, and their pharmacological profile is shown in Table 1.
	Figure 2. Mono sulfated steroids are derived from marine sources, and their pharmacological profile is shown in Table 2.
	Figure 3. Mono sulfated steroids are derived from marine sources, and their pharmacological profile is shown in Table 3.
	Figure 4. Mono- and poly-sulfated steroids derived from marine sources, and their pharmacological profile, are shown in Table 4.
	Figure 5. Polysulfated steroids derived from marine sources, and their pharmacological profile is shown in Table 4.
	Figure 6. Sulfur-containing steroids and triterpenoids derived from marine invertebrates, sediments, crude oil, and other sources, and their pharmacological profile is shown in Table 5.
	Figure 7. Sulfur-containing steroids and triterpenoids derived from marine sediments, crude oil, and other sources, and their pharmacological profile is shown in Table 6.
	Figure 8. Sulfur-containing steroids and triterpenoids derived from marine sediments, crude oil, and other sources, and their pharmacological profile is shown in Table 7.
	Figure 9. Semi-synthetic and synthetic epithio steroids, and their pharmacological profile is shown in Table 8.
	Figure 10. The 3D graph shows the predicted and calculated antitumor activity of selected sulfated steroids (compound numbers: 28, 29, 40, 42, 43, 44, 45, 48, and 64) showing the highest degree of confidence, more than 91%. These sulfated steroids derived from marine sources can be used in clinical medicine as agents with strong antitumor activity.
	Figure 11. 3D column graph of sulfated steroids derived from marine sources that show anti-hypercholesterolemic activity. The letters represent the steroid numbers shown in Figure 1, Figure 2, Figure 3 and Figure 4 and Table 1, Table 2, Table 3, Table 4 and Table 5: A—(1), B—(14), C—(16), D—(18), E—(19), F—(20), G—(21), H—(23), I—(24), J—(26), K—(31), L—(40), M—(41), N—(42), O—(43), and P—(52). Steroids that belong to this group, according to the data obtained by the PASS, have confirmed more than 90% of their biological activity.
	Figure 12. The 3D graph shows the predicted and calculated wound-healing activity of selected sulfated steroids (compound numbers: 14 (95.5%), 18 (93.8%), 19 (95.2%), 21 (92.8%), 29 (96.5%), 40 (95.3%), 41 (96.3%), 42 (97.5%), 43 (98.0%), 44 (97.7%), 60 (93.3%), and 61 (94.2%). These sulfated steroids show the highest degree of confidence, more than 92%.
	Figure 13. The 3D graph shows the predicted and calculated antitumor activity of selected sulfur-containing steroids (compound numbers): 98 (94.7%), 99 (94.7%), 100 (92.8%) and 105 (93.3%). These steroids show the highest degree of confidence, more than 92%.
	Figure 14. The 3D Graph (X and Y views) predicted and calculated activities of the spironolactone, which was isolated from the human urine extracts. According to PASS data, this steroid demonstrated seventeen different activities, with five activities having confidence of more than 90%. The main pharmacological properties and activities of spironolactone (73) are diuretic (99.1%), anti-hyperaldosteronism (96.3%), anti-hypertensive (94%), renal disease treatment (93.4%), and heart failure treatment (91.2%). As shown in numerous publications, spironolactone demonstrates properties as a potential diuretic, antihypertensive agent, or agent for the treatment of renal failure and heart failure, as well as an agent in the treatment of hyperaldosteronism (including Conn’s syndrome) and female hirsutism (due to additional antiandrogenic actions). All these properties and activities are confirmed by the PASS data as shown in this figure and shown in Table 5.
	Figure 15. The 3D graph shows the predicted and calculated antitumor activity of selected semi- and synthetic epithio steroids (compound numbers): 122 (96.4%), 123 (96.6%), 124 (96.6%), 125 (93.2%), 126 (95.5%), 127 (96.2%), 128 (97.1%), 129 (97.0%), 131 (96.0%), 132 (93.9%), 133 (97.4%), and 138 (91.2%). These steroids show the highest degree of confidence, more than 91%.
	Figure 16. The 3D graph shows the predicted and calculated anti-secretoric activity of some an epithio steroids (compound numbers): 122 (94.8%), 123 (95.2%), 124 (95.2%), 126 (93.8%), 130 (90.6%), 131 (96.5%), and 132 (96.7%). These epithio steroids show the highest degree of confidence, more than 90%.

Abbate, Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health. 2015, Pubmed

Abbate, Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health. 2015, Pubmed
Aiello, New cytotoxic steroids from the marine sponge Dysidea fragilis coming from the lagoon of Venice. 1995, Pubmed
Ajikumar, Terpenoids: opportunities for biosynthesis of natural product drugs using engineered microorganisms. 2008, Pubmed
Almeida, Antifouling potential of Nature-inspired sulfated compounds. 2017, Pubmed
Amiranashvili, Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies. 2020, Pubmed
Aufartová, Determination of steroid hormones in biological and environmental samples using green microextraction techniques: an overview. 2011, Pubmed
Berdyshev, Mass spectrometry of fatty aldehydes. 2011, Pubmed
Björkman, The identification of large amounts of cerebroside and cholesterol sulfate in the sea star, Asterias rubens. 1972, Pubmed , Echinobase
Brown, On the Connection between Chemical Constitution and Physiological Action; with special reference to the Physiological Action of the Salts of the Ammonium Bases derived from Strychnia, Brucia, Thebaia, Codeia, Morphia, and Nicotia. 1868, Pubmed
Carone, Spironolactone. 2017, Pubmed
Carvalhal, SULFATION PATHWAYS: Sources and biological activities of marine sulfated steroids. 2018, Pubmed
Chen, Topsensterols A-C, Cytotoxic Polyhydroxylated Sterol Derivatives from a Marine Sponge Topsentia sp. 2016, Pubmed
Chen, Transformation of sulfur species in lake sediments at Ardley Island and Fildes Peninsula, King George Island, Antarctic Peninsula. 2020, Pubmed
Chludil, Minutosides A and B, antifungal sulfated steroid xylosides from the patagonian starfish Anasterias minuta. 2005, Pubmed , Echinobase
Colussi, Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension. 2013, Pubmed
Comin, Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs. 1999, Pubmed , Echinobase
Correia-da-Silva, Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration. 2014, Pubmed
Cranwell, Lipids of aquatic sediments and sedimenting particulates. 1982, Pubmed
Cunha, Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications. 2016, Pubmed
Darnet, Metabolism and Biological Activities of 4-Methyl-Sterols. 2019, Pubmed
Dembitsky, Chemistry and biodiversity of the biologically active natural glycosides. 2004, Pubmed
Dembitsky, Antitumor and hepatoprotective activity of natural and synthetic neo steroids. 2020, Pubmed
Dembitsky, Natural and synthetic small boron-containing molecules as potential inhibitors of bacterial and fungal quorum sensing. 2011, Pubmed
Dembitsky, Betaine ether-linked glycerolipids: chemistry and biology. 1996, Pubmed
Dembitsky, Natural halogenated fatty acids: their analogues and derivatives. 2002, Pubmed
Dembitsky, Quantification of plasmalogen, alkylacyl and diacyl glycerophospholipids by micro-thin-layer chromatography. 1988, Pubmed
Dembitsky, Naturally occurring aromatic steroids and their biological activities. 2018, Pubmed
Dembitsky, Astonishing diversity of natural surfactants: 5. Biologically active glycosides of aromatic metabolites. 2005, Pubmed
Dembitsky, Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity. 2021, Pubmed
Díaz,  Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis. NULL, Pubmed
Ermolenko, Chemical Diversity of Soft Coral Steroids and Their Pharmacological Activities. 2020, Pubmed
Gallo, Autoinhibitory sterol sulfates mediate programmed cell death in a bloom-forming marine diatom. 2017, Pubmed
Gunasekera, Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites. 1994, Pubmed
Harris, The fate of microplastic in marine sedimentary environments: A review and synthesis. 2020, Pubmed
Horishny, 3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation. 2020, Pubmed
Ichihashi, Absorption and disposition of epithiosteroids in rats (2): Avoidance of first-pass metabolism of mepitiostane by lymphatic absorption. 1991, Pubmed
Imperatore, Phallusiasterols A and B: two new sulfated sterols from the Mediterranean tunicate Phallusia fumigata and their effects as modulators of the PXR receptor. 2014, Pubmed
Iorizzi, Chemical and biological investigation of the polar constituents of the starfish Luidia clathrata, collected in the Gulf of Mexico. 1995, Pubmed , Echinobase
Ivanchina, Highly hydroxylated steroids of the starfish Archaster typicus from the Vietnamese waters. 2010, Pubmed , Echinobase
Ivanchina, Granulatosides D, E and other polar steroid compounds from the starfish Choriaster granulatus. Their immunomodulatory activity and cytotoxicity. 2019, Pubmed , Echinobase
Ivanchina, Hemolytic polar steroidal constituents of the starfish Aphelasterias japonica. 2000, Pubmed , Echinobase
Izuo, A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer. 1985, Pubmed
Jørgensen, The Biogeochemical Sulfur Cycle of Marine Sediments. 2019, Pubmed
Karim, Isolation and identification of novel sulfur-containing metabolites of spironolactone (Aldactone). 1972, Pubmed
Kates, Lipid components of diatoms. 1966, Pubmed
Kellis, Inhibition of aromatase cytochrome P-450 by 10-oxirane and 10-thiirane substituted androgens. Implications for the structure of the active site. 1987, Pubmed
Kellner Filho, Bioactive Aliphatic Sulfates from Marine Invertebrates. 2019, Pubmed
Kicha, Polar steroid compounds from the Arctic starfish Asterias microdiscus and their cytotoxic properties against normal and tumor cells in vitro. 2021, Pubmed , Echinobase
Kornprobst, Sulfated compounds from marine organisms. 1998, Pubmed
Lamers, Microbial transformations of nitrogen, sulfur, and iron dictate vegetation composition in wetlands: a review. 2012, Pubmed
Lee, Secondary Metabolites from the Marine Sponges of the Genus Petrosia: A Literature Review of 43 Years of Research. 2021, Pubmed
Lee, Three New Cytotoxic Steroidal Glycosides Isolated from Conus pulicarius Collected in Kosrae, Micronesia. 2017, Pubmed
Levina, New ophiuroid-type steroids from the starfish pteraster tesselatus. 1998, Pubmed , Echinobase
Li, Progesterone receptor membrane component-1 regulates hepcidin biosynthesis. 2016, Pubmed
Makarieva, Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix. 1993, Pubmed , Echinobase
Makarieva, Steroids in Porifera. II. Steroid derivatives from two sponges of the family Halichondriidae. Sokotrasterol sulfate, a marine steroid with a new pattern of side chain alkylation. 1983, Pubmed
Malyarenko, Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities. 2015, Pubmed , Echinobase
McKee, HIV-inhibitory natural products. 11. Comparative studies of sulfated sterols from marine invertebrates. 1994, Pubmed , Echinobase
Mensah-Nyagan, In vivo evidence for the production of sulfated steroids in the frog brain. 2000, Pubmed
Mervin, Target prediction utilising negative bioactivity data covering large chemical space. 2015, Pubmed
Mougous, Sulfotransferases and sulfatases in mycobacteria. 2002, Pubmed
Mueller, The Regulation of Steroid Action by Sulfation and Desulfation. 2015, Pubmed
Muthukumar, Sulfated polysaccharides and its commercial applications in food industries-A review. 2021, Pubmed
Nakamura, Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria. 2018, Pubmed
Núñez-Pons, Marine Terpenoids from Polar Latitudes and Their Potential Applications in Biotechnology. 2020, Pubmed , Echinobase
Okano, Analysis of non-ketoic steroids 17alpha-methylepithiostanol and desoxymethyl- testosterone in dietary supplements. 2009, Pubmed
Palagiano, Isolation of 20 glycosides from the starfish Henricia downeyae, collected in the Gulf of Mexico. 1996, Pubmed , Echinobase
Pancost, Lipid biomolecules in silica sinters: indicators of microbial biodiversity. 2005, Pubmed
Patel, A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug-Drug Interactions with Orally Administered Medications. 2020, Pubmed
Pauli, Occurrence of progesterone and related animal steroids in two higher plants. 2010, Pubmed
Peng, Polyhydroxy steroids and saponins from China Sea starfish Asterina pectinifera and their biological activities. 2010, Pubmed , Echinobase
Petrov, Epistane, an anabolic steroid used for recreational purposes, causes cholestasis with elevated levels of cholic acid conjugates, by upregulating bile acid synthesis (CYP8B1) and cross-talking with nuclear receptors in human hepatocytes. 2020, Pubmed
Poroikov, [Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology]. 2020, Pubmed
Roy, Two new steroid sulfates from a cheilostome bryozoan, Calyptotheca sp. 2022, Pubmed
Sato, 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. 2001, Pubmed , Echinobase
Segar, Neonatal diuretic therapy: furosemide, thiazides, and spironolactone. 2012, Pubmed
Sheikh, Steroids from starfish. 1973, Pubmed , Echinobase
Shubina, Gracilosulfates A-G, Monosulfated Polyoxygenated Steroids from the Marine Sponge Haliclona gracilis. 2020, Pubmed
Sperry, Haliclostanone sulfate and halistanol sulfate from an Indo-Pacific Haliclona sponge. 1997, Pubmed
Stonik, Asterosaponins: Structures, Taxonomic Distribution, Biogenesis and Biological Activities. 2020, Pubmed , Echinobase
Stumpfe, Evolving Concept of Activity Cliffs. 2019, Pubmed
Suchański, [The biological role of sulfatides]. 2016, Pubmed
Summons, Lipid biomarkers for bacterial ecosystems: studies of cultured organisms, hydrothermal environments and ancient sediments. 1996, Pubmed
Takeda, Bile acids and steroids. XXVII. Thiosteroids (12) steroidal 2,3- and 3,4-episulphides and related compounds. 1965, Pubmed
Teles, Sulphated Flavonoids: Biosynthesis, Structures, and Biological Activities. 2018, Pubmed
Thao, Steroidal constituents from the edible sea urchin Diadema savignyi Michelin induce apoptosis in human cancer cells. 2015, Pubmed , Echinobase
Tsukamoto, Acanthosterol sulfates A-J: ten new antifungal steroidal sulfates from a marine sponge Acanthodendrilla sp. 1998, Pubmed
Vizer, Propargylic sulfides: synthesis, properties, and application. 2015, Pubmed
Volkman, Identification of natural, anthropogenic and petroleum hydrocarbons in aquatic sediments. 1992, Pubmed
Volkman, Sterols in microorganisms. 2003, Pubmed
Voogt, Biosynthesis and composition of 3 -sterols in the ophiuroids Ophiura albida and Ophioderma longicauda. 1973, Pubmed , Echinobase
Vázquez, Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches. 2020, Pubmed
Waller, In vivo metabolism of the designer anabolic steroid hemapolin in the thoroughbred horse. 2020, Pubmed
Weisskopf, Microbial volatile organic compounds in intra-kingdom and inter-kingdom interactions. 2021, Pubmed
Whitson, Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp. 2008, Pubmed
Whitson, Fibrosterol sulfates from the Philippine sponge Lissodendoryx (Acanthodoryx) fibrosa: sterol dimers that inhibit PKCzeta. 2009, Pubmed
Wolkenstein, Boron-containing organic pigments from a Jurassic red alga. 2010, Pubmed
Wolkenstein, Structure and Absolute Configuration of Jurassic Polyketide-Derived Spiroborate Pigments Obtained from Microgram Quantities. 2015, Pubmed
Yurchenko, Metabolites of Marine Sediment-Derived Fungi: Actual Trends of Biological Activity Studies. 2021, Pubmed
Zamanpour, Gas ebullition from petroleum hydrocarbons in aquatic sediments: A review. 2020, Pubmed
de Marvao, Heart disease in women: a narrative review. 2021, Pubmed