Applied Microbiology and Biotechnology

, Volume 102, Issue 18, pp 7657–7667 | Cite as

Peroxy steroids derived from plant and fungi and their biological activities

  • Vera A. Vil
  • Tatyana A. Gloriozova
  • Vladimir V. Poroikov
  • Alexander O. Terent’ev
  • Nick Savidov
  • Valery M. DembitskyEmail author


Peroxides represent a large and interesting group of biologically active natural compounds. All these metabolites contain a peroxide group (R-O-O-R). This review describes studies of more than 60 peroxides isolated from plants and fungi. Most of the plant peroxy steroids exhibit high antiprotozoal (Plasmodium) activity with a confidence of up to 95%, while steroids harvested from fungi show more antineoplastic activity with a confidence of up to 94%. In addition, more than 20 different activities of both groups of peroxides with a probability of 78 to 90% have also been predicted using computer program PASS.


Peroxides Plants Fungi Pharmacological activities 



The work was performed in the framework of the Program for Basic Research of Russian State Academies of Sciences for 2013–2020.

Compliance with ethical

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Ananikov VP, Khemchyan LL, Ivanova YV, Bukhtiyarov VI, Sorokin AM (2014) Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision. Russ Chem Rev 83(10):885–985CrossRefGoogle Scholar
  2. Asai T, Hara N, Fujimoto Y (2010) Fatty acid derivatives and dammarane triterpenes from the glandular trichome exudates of Ibicella lutea and Proboscidea louisiana. Phytochemistry 71:877–794CrossRefPubMedGoogle Scholar
  3. Bar FMA, Zaghloul AM, Bachawal SV, Sylvester PW, Ahmad KF, El Sayed KA (2008) Antiproliferative triterpenes from Melaleuca ericifolia. J Nat Prod 71:1787–1792CrossRefPubMedGoogle Scholar
  4. Barlow RB (1979-1980) Structure-activity relationships. Trends Pharmacol Sci 1(1):109–111CrossRefGoogle Scholar
  5. Bezhentsev VM, Druzhilovskiy DS, Ivanov SM, Filimonov DA, Sastry GN, Poroikov VV (2017) Web resources for discovery and development of new medicines. Pharm Chem J 51(2):91–99CrossRefGoogle Scholar
  6. Bok JW, Lermer L, Chilton J, Klingeman GH, Towers N (1999) Antitumor sterols from the mycelia of Cordyceps sinensis. Phytochemistry 51:891–898CrossRefPubMedGoogle Scholar
  7. Cabrera GM, Seldes AM (1995) Hydroperoxycycloartanes from Tillandsia recurvata. J Nat Prod 58:1920–1924CrossRefGoogle Scholar
  8. Casteel DA (1992) Peroxy natural products. Nat Prod Rep 9:289–312CrossRefPubMedGoogle Scholar
  9. Casteel DA (1999) Peroxy natural products. Nat Prod Rep 16:55–73CrossRefGoogle Scholar
  10. Chen JJ, Fei DQ, Chen SG, Gao K (2008) Antimicrobial triterpenoids from Vladimiria muliensis. J Nat Prod 71:547–550CrossRefPubMedGoogle Scholar
  11. Chen JX, Chen JC, Sun Y, Yan YX, Kong LM, Li Y, Qiu MH (2011) Five new diarylpropan-1-ols from Combretum yunnanense. Planta Med 77:1841–1844CrossRefPubMedGoogle Scholar
  12. Chiamg YM, Kuo YH (2001) New peroxy triterpenes from the aerial roots of Ficus microcarpa. J Nat Prod 64:436–439CrossRefGoogle Scholar
  13. Chiang YM, Kuo YH (2008) Taraxastane-type triterpenes from the aerial roots of Ficus microcarpa. J Nat Prod 63:898–901CrossRefGoogle Scholar
  14. Cirigliano AM, Veleiro AS, Oberti JC, Burton G (2002) Spiranoid withanolides from Jaborosa odonelliana. J Nat Prod 65:1049–1054CrossRefPubMedGoogle Scholar
  15. Clark DE (2001) Peroxides and peroxide forming compounds. Chem Health Saf 8:12–22CrossRefGoogle Scholar
  16. Comyns AE (1996) Peroxides and peroxide compounds, inorganic peroxides. In: Kirk-Othmer encyclopedia of chemical technology. WileyGoogle Scholar
  17. Della Greca M, Fiorentino A, Molinaro A, Monaco P, Previtera L (1994) Hydroperoxysterols in Arum italicum. Nat Prod Lett 5:7–14CrossRefGoogle Scholar
  18. Dembitsky VM (1992) Lipids of lichens. Prog Lipid Res 31(4):373–397CrossRefPubMedGoogle Scholar
  19. Dembitsky VM (1996) Betaine ether-linked glycerolipids: chemistry and biology. Prog Lipid Res 35(1):1–51CrossRefPubMedGoogle Scholar
  20. Dembitsky VM (2003) Oxidation, epoxidation and sulfoxidation reactions catalysed by haloperoxidases. Tetrahedron 59(26):4701–4720CrossRefGoogle Scholar
  21. Dembitsky VM (2008a) Bioactive peroxides as potential therapeutic agents. Eur J Med Chem 43(2):223–251CrossRefPubMedGoogle Scholar
  22. Dembitsky VM (2008b) Bioactive cyclobutane-containing alkaloids. J Nat Med 62(1):1–33CrossRefPubMedGoogle Scholar
  23. Dembitsky VM (2014) Naturally occurring bioactive cyclobutane-containing (CBC) alkaloids in fungi, fungal endophytes, and plants. Phytomedicine 21(12):1559–1581CrossRefPubMedGoogle Scholar
  24. Dembitsky VM (2015a) Bioactive fungal endoperoxides. Med Mycol 1(5):1–7Google Scholar
  25. Dembitsky VM (2015b) Astonishing diversity of natural peroxides as potential therapeutic agents. J Mol Genet Med 9:1–18Google Scholar
  26. Dembitsky VM (2017a) The multiple properties of some of the lichenized ascomycetes: biological activity and active metabolites. In: Plant adaptation strategies in changing environment. Springer Verlag: Singapore. Chapter 8, pp. 201–234Google Scholar
  27. Dembitsky VM (2017b) Paradigm shifts in fungal secondary metabolite research: unusual fatty acids incorporated into fungal peptides. Int J Current Res Biosci Plant Biol 4(12):7–29CrossRefGoogle Scholar
  28. Dembitsky VM, Gloriozova TA (2017) Naturally occurring boron containing compounds and their biological activities. Journal of Natural Products and Resources (India) 3(2):147–154Google Scholar
  29. Dembitsky VM, Levitsky DO (2004) Arsenolipids. Prog Lipid Res 43(5):403–448CrossRefPubMedGoogle Scholar
  30. Dembitsky VM, Srebnik M (2002) Natural halogenated fatty acids: their analogues and derivatives. Prog Lipid Res 41(4):315–367CrossRefPubMedGoogle Scholar
  31. Dembitsky VM, Rezanka T, Bychek IA, Shustov MV (1991) Identification of fatty acids from Cladonia lichens. Phytochemistry 30(12):4015–4018CrossRefGoogle Scholar
  32. Dembitsky VM, Rezanka T, Bychek IA, Shustov MV (1992) Fatty acid composition of Parmelia lichens. Phytochemistry 31(3):841–843CrossRefGoogle Scholar
  33. Dembitsky VM, Gloriozova TA, Poroikov VV (2007) Natural peroxy anticancer agents. Mini-Rev Med Chem 7(6):571–589CrossRefPubMedGoogle Scholar
  34. Dembitsky V, Shkrob I, Hanus LO (2008) Ascaridole and related peroxides from the genus Chenopodium. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 152(2):209–215CrossRefPubMedGoogle Scholar
  35. Dembitsky VM, Al Quntar AAA, Srebnik M (2011) Natural and synthetic small boron-containing molecules as potential inhibitors of bacterial and fungal quorum sensing. Chem Rev 111(1):209–237CrossRefPubMedGoogle Scholar
  36. Ding Y, Liang C, Kim JH, Lee YM, Hyun JH, Kang HK, Kim JA, Min BS, Kim YH (2010) Triterpene compounds isolated from Acer mandshuricum and their anti-inflammatory activity. Bioorg Med Chem Lett 20:1528–1531CrossRefPubMedGoogle Scholar
  37. Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskiy DS, Pogodin PV, Poroikov VV (2014) Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem Heterocycl Compd 50(3):444–457CrossRefGoogle Scholar
  38. Filimonov DA, Druzhilovskiy DS, Lagunin AA, Gloriozova TA, Rudik AV, Dmitriev AV, Pogodin PV, Poroikov VV (2018) Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitations. Biom Chem Res Method 1(1):e00004CrossRefGoogle Scholar
  39. Fischer FG, Magerlein H (1960) Zur natürlichen Photooxydation von Sterinen. Ein Stigmastentriol und ein Hydroperoxy-stigmastendiol in den Blättern der Rosskastanie. Liebigs Ann Chem 636:88–94CrossRefGoogle Scholar
  40. Goel RK, Gawande DY, Lagunin AA, Poroikov V (2018) Pharmacological repositioning of Achyranthes aspera as antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation. SAR QSAR Environ Res 29(1):69–81CrossRefPubMedGoogle Scholar
  41. Green BJ, Beezhold DH (2011) Industrial fungal enzymes: an occupational allergen perspective. J Allergy 682574:1–11. CrossRefGoogle Scholar
  42. He F, Pu JX, Huang SX, Wang YY, Xiao WL, Li LM, Liu JP, Zhang HB, Li Y, Sun HD (2010) Schinalactone A, a new cytotoxic triterpenoid from Schisandra sphenanthera. Org Lett 12:1208–1211CrossRefPubMedGoogle Scholar
  43. Herz W, Watanabe K, Kulanthaivel P, Blount JF (1985) Cycloartanes from Lindheimera texana. Phytochemistry 24:2645–2654CrossRefGoogle Scholar
  44. Huang HC, Liaw CC, Yang HL, Hseu YC, Kuo HT (2012) Lanostane triterpenoids and sterols from Antrodia camphorata. Phytochemistry 84:177–183CrossRefPubMedGoogle Scholar
  45. Inada A, Murata K, Inatomi Y, Nakanishi T, Darnaed D (1997) Pregnanes and triterpenoid hydroperoxides from the leaves of Aglaia grandis. Phytochemistry 45:1225–1228CrossRefGoogle Scholar
  46. Ismail FMD, Levitsky DO, Dembitsky VM (2009) Aziridine alkaloids as potential therapeutic agents. Eur J Med Chem 44(9):3373–3387CrossRefPubMedGoogle Scholar
  47. Jefford CW (2012) Synthetic peroxides as potent antimalarials. News and views. Curr Top Med Chem 12(5):373–399CrossRefPubMedGoogle Scholar
  48. Kato T, Frei B, Heinrich M, Sticher O (1996) Antibacterial hydroperoxysterols from Xanthosoma robustum. Phytochemistry 41:1191–1195CrossRefPubMedGoogle Scholar
  49. Khursan S, Antonovsky V (2005) Physical chemistry of organic peroxides. Taylor & Francis, Milton Park, p 550Google Scholar
  50. Klussmann M (2018) Alkenyl and aryl peroxides. Chemistry 24(18):4480–4496CrossRefPubMedGoogle Scholar
  51. Kuklev DV, Domb AJ, Dembitsky VM (2013) Bioactive acetylenic metabolites. Phytomedicine 20(13):1145–1159CrossRefPubMedGoogle Scholar
  52. Kyasa SK (2015) New methods for synthesis of organic peroxides and application of peroxide electrophiles to synthesis of functionalized ethers. Dissertation. University of Nebraska-LincolnGoogle Scholar
  53. Lagunin AA, Goel RK, Gawande DY, Priynka P, Gloriozova TA, Dmitriev AV, Ivanov SM, Rudik AV, Konova VI, Pogodin PV, Druzhilovsky DS, Poroikov VV (2014) Chemo- and bioinformatics resources for in silico drug discovery from medicinal plants beyond their traditional use: a critical review. Nat Prod Rep 31(11):1585–1611CrossRefPubMedGoogle Scholar
  54. Lee D, Cuendet M, Axelrod F, Chavez PI, Fong HHS, Pezzuto JM, Kinghorn AD (2001) Novel 29-nor-3,4-seco-cycloartane triterpene methyl esters from the aerial parts of Antirhea acutata. Tetrahedron 57:7107–7112CrossRefGoogle Scholar
  55. Liu DZ, Liu JK (2013) Peroxy natural products. Nat Prod Bioprospect 3(5):161–206CrossRefPubMedCentralGoogle Scholar
  56. Liu D, Li XM, Li CS, Wang BG (2013) Nigerasterols A and B, antiproliferative sterols from the mangrove-derived endophytic fungus Aspergillus niger MA-132. Helv Chim Acta 96(6):1055–1061CrossRefGoogle Scholar
  57. Ma YP, Li N, Gao J, Fu KL, Qin Y, Li GY, Wang JH (2011) A new peroxy-multiflorane triterpene ester from the processed seeds of Trichosanthes kirilowii. Helv Chim Acta 94:1881–1887CrossRefGoogle Scholar
  58. Makino B, Kawai M, Iwata Y, Yamamura H, Butsugan Y, Ogawa K, Hayashi M (1995) Physalins possessing an endoperoxy structure from Physalis alkekengi var. francheti. Structural revision of physalin K. Bull Chem Soc Jpn 68:219–223CrossRefGoogle Scholar
  59. Mallavadhani UV, Sudhakar AVS, Satyanarayana KVS, Mahapatra A, Li W, Van Breemen RB (2006) Chemical and analytical screening of some edible mushrooms. Food Chem 95(7):58–64CrossRefGoogle Scholar
  60. Merdivan S, Lindequist U (2017) Ergosterol peroxide: a mushroom-derived compound with promising biological activities—a review. Int J Med Mushrooms 19(2):93–105CrossRefPubMedGoogle Scholar
  61. Miao FP, Li XD, Liu XH, Cichewicz RH, Ji NY (2012) Secondary metabolites from an algicolous Aspergillus versicolor strain. Mar Drugs 10:131–139CrossRefPubMedPubMedCentralGoogle Scholar
  62. Murtazalieva KA, Druzhilovskiy DS, Goel RK, Sastry GN, Poroikov VV (2017) How good are publicly available web services that predict bioactivity profiles for drug repurposing? SAR QSAR Environ Res 28(10):843–862CrossRefPubMedGoogle Scholar
  63. Nakatani N, Kikuzaki H, Yamaji H, Yoshio K, Kitora C, Okada K, Padolina WG (1994) Labdane diterpenes from rhizomes of Hedychium coronarium. Phytochemistry 37:1383–1388CrossRefGoogle Scholar
  64. Öksüz S, Gil RR, Chai H, Pezzuto JM, Cordell GA, Ulubelen A (1994) Biologically active compounds from the Euphorbiaceae. 2. Two triterpenoids of Euphorbia cyparissias. Planta Med 60:594–595CrossRefPubMedGoogle Scholar
  65. Østergaard LH, Olsen HS (2011) Industrial applications of fungal enzymes. In: Hofrichter M (ed) Industrial applications. Springer, BerlinGoogle Scholar
  66. Rocha MR, de Souza JJ, Barcellos LT, Sant'Anna CM, Braz-Filho R, Vieira IJ (2014) A novel 3,9-(1,2,3-trioxocine)-type steroid of Rauia nodosa (Rutaceae). Molecules 19(9):14637–14648CrossRefPubMedGoogle Scholar
  67. Saha B, Naskar DB, Misra DR, Pradhan BP, Khastgir HN (1977) Baccatin, a novel nor-triterpene peroxide isolated from Sapium baccatum roxb. Tetrahedron Lett 18(35):3095–3098CrossRefGoogle Scholar
  68. Serebryakov EP, Simolin AV, Kucherov VF, Rosynov BV (1970) New metabolites of Fusarium moniliforme sheld. Tetrahedron 26:5215–5219CrossRefGoogle Scholar
  69. Shi XW, Li XJ, Gao JM, Zhang XC (2011) Fasciculols H and I, two lanostane derivatives from Chinese mushroom Naematoloma fasciculare. Chem Biodivers 8:1864–1870CrossRefPubMedGoogle Scholar
  70. Song QY, Jiang K, Zhao QQ, Gao K, Jin XJ, Yao XJ (2013) Eleven new highly oxygenated triterpenoids from the leaves and stems of Schisandra chinensis. Org Biomol Chem 11:251–258Google Scholar
  71. Sy LK, Brown GD (1997) Labdane diterpenoids from Alpinia chinensis. J Nat Prod 60:904–908CrossRefGoogle Scholar
  72. Tan JM, Qiu YH, Tan XQ, Tan CH (2011) Three new peroxy triterpene lactones from Pseudolarix kaempferi. Helv Chim Acta 94:1697–1702CrossRefGoogle Scholar
  73. Terent'ev AO, Platonov MM, Levitsky DO, Dembitsky VM (2011) Organosilicon and organogermanium peroxides: synthesis and reactions. Russ Chem Rev 80(9):807–828CrossRefGoogle Scholar
  74. Terent'ev AO, Borisov DA, Vil' VA, Dembitsky VM (2014) Synthesis of five- and six-membered cyclic organic peroxides: key transformations into peroxide ring-retaining products. Beilstein J Org Chem 10:34–114CrossRefPubMedPubMedCentralGoogle Scholar
  75. Uchiyama T, Hara S, Makino M, Fujimoto Y (2002) Seco-Adianane-type triterpenoids from Dorstenia brasiliensis (Moraceae). Phytochemistry 60(8):761–764CrossRefPubMedGoogle Scholar
  76. Van Der Vijver LM (1974) Distribution of plumbag in in the Plumbaginaceae. Phytochemistry. 11:3247–3248Google Scholar
  77. Vazdekis NEJ, Chavez H, Estevez-Braun A, Ravelo AG (2009) Triterpenoids and a lignan from the aerial parts of Maytenus apurimacensis. J Nat Prod 72:1045–1048CrossRefPubMedGoogle Scholar
  78. Vil' VA, Yaremenko IA, Ilovaisky AI, Terent'ev AO (2017) Peroxides with anthelmintic, antiprotozoal, fungicidal and antiviral bioactivity: properties, synthesis and reactions. Molecules 22(11):1881. CrossRefGoogle Scholar
  79. Wang F, Fang Y, Zhang M, Lin A, Zhu T, Gu Q, Zhu W (1991) Six new ergosterols from the marine-derived fungus Rhizopus sp. Comp Biochem Physiol 100B(3):647–651Google Scholar
  80. Wang P, Qin HL, Zhang L, Li ZH, Wang YH, Zhu HB (2004) Steroids from the roots of Cynanchum stauntonii. Planta Med 70(11):1075–1079CrossRefPubMedGoogle Scholar
  81. Wautie A (1946) Prophylaxis and treatment of the chief parasitic diseases of the gastrointestinal tract of the horse. Parasitica 2:44–67Google Scholar
  82. Wu QX, Liu X, Shi YP (2007) Chemical components from Gentiana aristata. Chem Biodivers 4:175–182CrossRefPubMedGoogle Scholar
  83. Wu SB, Bao QY, Wang WX, Zhao Y, Xia G, Zhao Z, Zeng H, Hu JF (2011) Cytotoxic triterpenoids and steroids from the bark of Melia azedarach. Planta Med 77(9):922–928CrossRefPubMedGoogle Scholar
  84. Yaoita Y, Amemiya K, Ohnuma H, Furumura K, Masaki A, Matasuki T, Kikuchi M (1998) Sterol constituents from five edible mushrooms. Chem Pharm Bull 46:944–950CrossRefGoogle Scholar
  85. Yaoita Y, Matsuki K, Iijima T, Nakano S, Kakuda R, Machida K, Kikuchi M (2001) New sterols and triterpenoids from four edible mushrooms. Chem Pharm Bull 49:589–594CrossRefPubMedGoogle Scholar
  86. Yaoita Y, Yoshihara Y, Kakuda R, Machida K, Kikuchi M (2002) New sterols from two edible mushrooms, Pleurotus eryngii and Panellus serotinus. Chem Pharm Bull 50:551–553CrossRefPubMedGoogle Scholar
  87. Yaremenko IA, Vil’ VA, Demchuk DV, Terent’ev AO (2016) Rearrangements of organic peroxides and related processes. Beilstein J Org Chem 12:1647–1748CrossRefPubMedPubMedCentralGoogle Scholar
  88. Yue JM, Chen SN, Lin ZW, Sun HD (2001) Sterols from the fungus Lactarium volemus. Phytochemistry 56:801–806CrossRefPubMedGoogle Scholar
  89. Zang M, Ying JZ (1994) Economic fungi in the South West of China. Scientific Press, BeijingGoogle Scholar
  90. Zhang Y, Pei L, Gao L, Huang Q, Qi J (2011) A neuritogenic compound from Tremella fuciformis. Zhongguo Zhong Yao Za Zhi 36:2358–2360PubMedGoogle Scholar
  91. Zheng W, Liu T, Xiang X, Gu Q (2007) Sterol composition in field-grown and cultured mycelia of Inonotus obliquus. Yaoxue Xuebao 42:750–756Google Scholar
  92. Zhou T, Zhang H, Zhu N, Chiu P (2004) New triterpene peroxides from Pseudolarix kaempferi. Tetrahedron 60:4931–4936CrossRefGoogle Scholar
  93. Zuo W, Luo DQ (2010) Research on the chemical components of the fruit bodies of Boletus calopus. Anhui Nongye Kexue 38:2356–2357Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Vera A. Vil
    • 1
  • Tatyana A. Gloriozova
    • 2
  • Vladimir V. Poroikov
    • 2
  • Alexander O. Terent’ev
    • 1
  • Nick Savidov
    • 3
  • Valery M. Dembitsky
    • 3
    • 4
    Email author
  1. 1.N.D. Zelinsky Institute of Organic ChemistryRussian Academy of SciencesMoscowRussia
  2. 2.Institute of Biomedical ChemistryMoscowRussia
  3. 3.Centre for Applied Research and InnovationLethbridge CollegeLethbridgeCanada
  4. 4.Biochemistry Lab, National Scientific Center of Marine BiologyVladivostokRussia

Personalised recommendations