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Current Topics in Medicinal Chemistry

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Review Article

Phenanthrene Dimers: Promising Source of Biologically Active Molecules

Author(s): Antonino De Natale, Antonino Pollio, Anna De Marco, Giovanni Luongo, Giovanni Di Fabio and Armando Zarrelli*

Volume 22, Issue 11, 2022

Published on: 13 August, 2021

Page: [939 - 956] Pages: 18

DOI: 10.2174/1568026621666210813113918

Price: $65

Abstract

To date, just over a hundred phenanthrenoid dimers have been isolated. Of these, forty-two are completely phenanthrenic in nature. They are isolated from fourteen genera of different plants belonging to only five families, of which Orchidaceae is the most abundant source. Other nine completely acetylated and five methylated dimers were also defined, which were effective in establishing the position of the free hydroxyls of the corresponding natural products, from which they were obtained by semi-synthesis. Structurally, they could be useful chemotaxonomic markers considering that some substituents are typical of a single-family, such as the vinyl group for Juncaceae. From a biogenetic point of view, it is thought that these compounds derive from the radical coupling of the corresponding phenanthrenes or by dehydrogenation of the dihydrophenanthrenoid analogs. Phenanthrenes or dihydroderivatives possess different biological activities, e.g., antiproliferative, antimicrobial, antiinflammatory, antioxidant, spasmolytic, anxiolytic, and antialgal effects. The aim of this review is to summarize the occurrence of phenanthrene dimers in the different natural sources and give a comprehensive overview of their structural characteristics and biological activities.

Keywords: Dimeric phenanthrenes, Phenanthrenes, Phenanthraquinones, Biphenanthrene derivatives, Pharmacological activities, Antineuroinflammatory activity.

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[1]
Menezes, J.C.J.M.D.S.; Diederich, M.F. Natural dimers of coumarin, chalcones, and resveratrol and the link between structure and pharmacology. Eur. J. Med. Chem., 2019, 182, 111637.
[http://dx.doi.org/10.1016/j.ejmech.2019.111637] [PMID: 31494471]
[2]
Sun, J.; Yang, H.; Tang, W. Recent advances in total syntheses of complex dimeric natural products. Chem. Soc. Rev., 2021, 50(4), 2320-2336.
[http://dx.doi.org/10.1039/D0CS00220H] [PMID: 33470268]
[3]
Romanucci, V.; Gravante, R.; Cimafonte, M.; Marino, C.D.; Mailhot, G.; Brigante, M.; Zarrelli, A.; Fabio, G.D. Phosphate-linked silibinin dimers (PLSD): New promising modified metabolites. Molecules, 2017, 22(8), 1323.
[http://dx.doi.org/10.3390/molecules22081323] [PMID: 28800072]
[4]
Romanucci, V.; Di Fabio, G.; Zarrelli, A. A New class of synthetic flavonolignan-like dimers: Still few molecules, but with attractive properties. Molecules, 2018, 24(1), 108.
[http://dx.doi.org/10.3390/molecules24010108] [PMID: 30597952]
[5]
Rivière, C.; Pawlus, A.D.; Mérillon, J.M. Natural stilbenoids: distribution in the plant kingdom and chemotaxonomic interest in Vitaceae. Nat. Prod. Rep., 2012, 29(11), 1317-1333.
[http://dx.doi.org/10.1039/c2np20049j] [PMID: 23014926]
[6]
Auberon, F.; Olatunji, O.J.; Raminoson, D.; Muller, C.D.; Soengas, B.; Bonté, F.; Lobstein, A. Isolation of novel stilbenoids from the roots of Cyrtopodium paniculatum (Orchidaceae). Fitoterapia, 2017, 116, 99-105.
[http://dx.doi.org/10.1016/j.fitote.2016.11.015] [PMID: 27908799]
[7]
Tóth, B.; Hohmann, J.; Vasas, A. Phenanthrenes: A promising group of plant secondary metabolites. J. Nat. Prod., 2018, 81(3), 661-678.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00619] [PMID: 29280630]
[8]
Hertweck, K.L.; Kinney, M.S.; Stuart, S.A.; Maurin, O.; Mathews, S.; Chase, M.W.; Pires, J.C. Phylogenetics, divergence times and diversification from three genomic partitions in monocots. Bot. J. Linn. Soc., 2015, 178(3), 375-393.
[http://dx.doi.org/10.1111/boj.12260]
[9]
Crane, P.R.; Friis, E.M.; Pedersen, K.R. The origin and early diversification of angiosperms. Nature, 1995, 374, 27-33.
[http://dx.doi.org/10.1038/374027a0]
[10]
Guo, Y.Y.; Luo, Y.B.; Liu, Z.J.; Wang, X.Q. Evolution and biogeography of the slipper orchids: Eocene vicariance of the conduplicate genera in the Old and New World Tropics. PLoS One, 2012, 7(6), e38788.
[http://dx.doi.org/10.1371/journal.pone.0038788] [PMID: 22685605]
[11]
Djordjević, V.; Tsiftsis, S.; Lakušić, D.; Jovanović, S.; Jakovljević, K.; Stevanović, V. Patterns of distribution, abundance and composition of forest terrestrial orchids. Biodivers. Conserv., 2020, 29(14), 4111-4134.
[http://dx.doi.org/10.1007/s10531-020-02067-6]
[12]
Chase, M.W.; Cameron, K.M.; Freudenstein, J.V.; Pridgeon, A.M.; Salazar, G.; Van den Berg, C.; Schuiteman, A. An updated classification of Orchidaceae. Bot. J. Linn. Soc., 2015, 177(2), 151-174.
[http://dx.doi.org/10.1111/boj.12234]
[13]
Benzing, D.H. Epiphytic vegetation: A profile and suggestions for future inquiries. Physiological ecology of plants of the wet tropics; Springer: Dordrecht, 1984, pp. 155-171.
[http://dx.doi.org/10.1007/978-94-009-7299-5_12]
[14]
Sut, S.; Maggi, F.; Dall’Acqua, S. Bioactive secondary metabolites from orchids (Orchidaceae). Chem. Biodivers., 2017, 14(11), e1700172.
[http://dx.doi.org/10.1002/cbdv.201700172] [PMID: 28771984]
[15]
Gantait, S.; Das, A.; Mitra, M.; Chen, J.T. Secondary metabolites in orchids: Biosynthesis, medicinal uses, and biotechnology. S. Afr. J. Bot., 2021, 139, 338-351.
[http://dx.doi.org/10.1016/j.sajb.2021.03.015]
[16]
Balslev, H. Juncaceae; Flora Neotropica, 1996, pp. 1-167.
[17]
Snogerup, S. A revision of Juncus subgen. Juncus (Juncaceae). Willdenowia, 1993, 23-73.
[18]
Syranidou, E.; Christofilopoulos, S.; Kalogerakis, N. Juncus spp.- The helophyte for all (phyto)remediation purposes? N. Biotechnol., 2017, 38(Pt B), 43-55.
[http://dx.doi.org/10.1016/j.nbt.2016.12.005] [PMID: 28040555]
[19]
El-Shamy, A.I.; Abdel-Razek, A.F.; Nassar, M.I. Phytochemical review of Juncus L. genus (Fam. Juncaceae). Arab. J. Chem., 2015, 8(5), 614-623.
[http://dx.doi.org/10.1016/j.arabjc.2012.07.007]
[20]
DellaGreca, M.; Fiorentino, A.; Monaco, P.; Previtera, L.; Temussi, F.; Zarrelli, A. New dimeric phe-nanthrenoids from the rhizomes of Juncus acutus. Structure determination and antialgal activity. Tetrahedron, 2003, 59(13), 2317-2324.
[http://dx.doi.org/10.1016/S0040-4020(03)00237-0]
[21]
DellaGreca, M.; Isidori, M.; Lavorgna, M.; Monaco, P.; Previtera, L.; Zarrelli, A. Bioactivity of phenanthrenes from Juncus acutus on Selenastrum capricornutum. J. Chem. Ecol., 2004, 30(4), 867-879.
[http://dx.doi.org/10.1023/B:JOEC.0000028437.96654.2c] [PMID: 15260229]
[22]
Della Greca, M.; Fiorentino, A.; Monaco, P.; Previtera, L.; Zarrelli, A. Effusides IV: 9,10-dihydrophenanthrene glucosides from Juncus effusus. Phytochemistry, 1995, 40(2), 533-535.
[http://dx.doi.org/10.1016/0031-9422(95)00287-H]
[23]
Bús, C.; Tóth, B.; Stefkó, D.; Hohmann, J.; Vasas, A. Family Juncaceae: Promising source of biologically active natural phenanthrenes. Phytochem. Rev., 2018, 17(4), 833-851.
[http://dx.doi.org/10.1007/s11101-018-9561-5]
[24]
DellaGreca, M.; Fiorentino, A.; Isidori, M.; Previtera, L.; Temussi, F.; Zarrelli, A. Benzocoumarins from the rhizomes of Juncus acutus. Tetrahedron, 2003, 59(26), 4821-4825.
[http://dx.doi.org/10.1016/S0040-4020(03)00698-7]
[25]
Adam, K.P.; Becker, H. Phenanthrenes and other phenolics from in vitro cultures of Marchantia polymorpha. Phytochemistry, 1994, 35, 139-143.
[http://dx.doi.org/10.1016/S0031-9422(00)90522-3]
[26]
Majumder, P.L.; Pal, A.; Joardar, M. Cirrhopetalanthrin, a dimeric phenanthrene derivative from the orchid Cirrhopetalum maculosum. Phytochemistry, 1990, 29, 271-274.
[http://dx.doi.org/10.1016/0031-9422(90)89048-E]
[27]
Majumder, P.L.; Lahiri, S. Volucrin, a new dimeric phenanthrene derivative from the orchid Lusia volucris. Tetrahedron, 1990, 46, 3621-3626.
[http://dx.doi.org/10.1016/S0040-4020(01)81531-3]
[28]
Majumder, P.L.; Banerjee, S.; Lahiri, S.; Mukhoti, N.; Sen, S. Dimeric phenanthrenes from two Agrostophyllum species. Phytochemistry, 1998, 47(5), 855-860.
[http://dx.doi.org/10.1016/S0031-9422(97)00667-5]
[29]
Tuchinda, P.; Udchachon, J.; Khumtaveeporn, K.; Taylor, W.C.; Engelhardt, L.M.; White, A.H. Phenanthrenes of Eulophia nuda. Phytochemistry, 1988, 27, 3267-3271.
[http://dx.doi.org/10.1016/0031-9422(88)80040-2]
[30]
Majumder, P.L.; Pal, S.; Majumder, S. Phenanthrene dimers from the orchid Bulbophyllum reptans. Phytochemistry, 1999, 50(5), 891-897.
[http://dx.doi.org/10.1016/S0031-9422(98)00609-8]
[31]
Thant, M.T.; Sritularak, B.; Chatsumpun, N.; Mekboonsonglarp, W.; Punpreuk, Y.; Likhitwitayawuid, K. Three novel biphenanthrene derivatives and a new phenylpropanoid ester from Aerides multiflora and their α-glucosidase inhibitory activity. Plants, 2021, 10(2), 385.
[http://dx.doi.org/10.3390/plants10020385] [PMID: 33671404]
[32]
Majumder, P.L.; Bandyopadhyay, S.; Pal, S. Rigidanthrin, a new dimeric phenanthrene derivative of the orchid Bulbophyllum rigidum. J. Indian Chem. Soc., 2008, 85(11), 1116-1123.
[33]
Leong, Y-W.; Harrison, L.J. A biphenanthrene and a phenanthro[4,3-b]furan from the orchid Bulbophyllum vaginatum. J. Nat. Prod., 2004, 67(9), 1601-1603.
[http://dx.doi.org/10.1021/np049909b] [PMID: 15387671]
[34]
Liu, L.; Li, J.; Zeng, K.W.; Jiang, Y.; Tu, P.F. Five new biphenanthrenes from Cremastra appendiculata. Molecules, 2016, 21(8), 1089.
[http://dx.doi.org/10.3390/molecules21081089] [PMID: 27548132]
[35]
Xue, Z.; Li, S.; Wang, S.; Wang, Y.; Yang, Y.; Shi, J.; He, L. Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata. J. Nat. Prod., 2006, 69(6), 907-913.
[http://dx.doi.org/10.1021/np060087n] [PMID: 16792409]
[36]
Sun, M.H.; Ma, X.J.; Shao, S.Y.; Han, S.W.; Jiang, J.W.; Zhang, J.J.; Li, S. Phenanthrene, 9,10-dihydrophenanthrene and bibenzyl enantiomers from Bletilla striata with their antineuroinflammatory and cytotoxic activities. Phytochemistry, 2021, 182, 112609.
[http://dx.doi.org/10.1016/j.phytochem.2020.112609] [PMID: 33326906]
[37]
Liu, X.Q.; Li, X.P.; Yuan, Q.Y. A new biphenanthrene glucoside from Cremastra appendiculata. Chem. Nat. Compd., 2015, 51(6), 1035-1037.
[http://dx.doi.org/10.1007/s10600-015-1484-4]
[38]
Liu, L.; Yin, Q.M.; Zhang, X.W.; Wang, W.; Dong, X.Y.; Yan, X.; Hu, R. Bioactivity-guided isolation of biphenanthrenes from Liparis nervosa. Fitoterapia, 2016, 115, 15-18.
[http://dx.doi.org/10.1016/j.fitote.2016.09.006] [PMID: 27642042]
[39]
Yamaki, M.; Bai, L.; Inoue, K.; Takagi, S. Biphenanthrenes from Bletilla striata. Phytochemistry, 1989, 28, 3503-3505.
[http://dx.doi.org/10.1016/0031-9422(89)80373-5]
[40]
Zhang, G-N.; Zhong, L-Y.; Bligh, S.W.A.; Guo, Y-L.; Zhang, C-F.; Zhang, M.; Wang, Z-T.; Xu, L-S. Bi-bicyclic and bi-tricyclic compounds from Dendrobium thyrsiflorum. Phytochemistry, 2005, 66(10), 1113-1120.
[http://dx.doi.org/10.1016/j.phytochem.2005.04.001] [PMID: 15913675]
[41]
Wang, C.; Shao, S.Y.; Han, S.W.; Li, S. Atropisomeric bi(9,10-dihydro)phenanthrene and phenanthrene/bibenzyl dimers with cytotoxic activity from the pseudobulbs of Pleione bulbocodioides. Fitoterapia, 2019, 138, 104313.
[http://dx.doi.org/10.1016/j.fitote.2019.104313] [PMID: 31421147]
[42]
Shi, Y.; Zhang, B.; Lu, Y.; Qian, C.; Feng, Y.; Fang, L.; Ding, Z.; Cheng, D. Antiviral activity of phenanthrenes from the medicinal plant Bletilla striata against influenza A virus. BMC Complement. Altern. Med., 2017, 17(1), 273.
[http://dx.doi.org/10.1186/s12906-017-1780-6] [PMID: 28532402]
[43]
Yang, M.; Cai, L.; Tai, Z.; Zeng, X.; Ding, Z. Four new phenanthrenes from Monomeria barbata Lindl. Fitoterapia, 2010, 81(8), 992-997.
[http://dx.doi.org/10.1016/j.fitote.2010.06.019] [PMID: 20600684]
[44]
Kyokong, N.; Muangnoi, C.; Thaweesest, W.; Kongkatitham, V.; Likhitwitayawuid, K.; Rojsitthisak, P.; Sritularak, B. A new phenanthrene dimer from Dendrobium palpebrae. J. Asian Nat. Prod. Res., 2019, 21(4), 391-397.
[http://dx.doi.org/10.1080/10286020.2018.1429416] [PMID: 29368951]
[45]
Qi, J.; Jiang, W.; Chen, G.; Zhou, D.; Li, N. Studies on the chemical components and biological activities of the genus of Juncus. J. Tradit. Med. (Toyama), 2020, 15(6), 375-393.
[46]
Ma, W.; Liu, F.; Ding, Y.Y.; Zhang, Y.; Li, N. Four new phenanthrenoid dimers from Juncus effusus L. with cytotoxic and anti-inflammatory activities. Fitoterapia, 2015, 105, 83-88.
[http://dx.doi.org/10.1016/j.fitote.2015.06.006] [PMID: 26072042]
[47]
Behery, F.A.; Naeem, Z.E.M.; Maatooq, G.T.; Amer, M.M.; Ahmed, A.F. A novel antioxidant phenanthrenoid dimer from Juncus acutus L. Nat. Prod. Res., 2013, 27(2), 155-163.
[http://dx.doi.org/10.1080/14786419.2012.662759] [PMID: 22360833]
[48]
Xiao, F.; Li, Q.; Tang, C.P.; Ke, C.Q.; Ye, Y.; Yao, S. Two new phenanthrenoid dimers from Juncus effusus. Chin. Chem. Lett., 2016, 27(11), 1721-1724.
[http://dx.doi.org/10.1016/j.cclet.2016.04.008]
[49]
Olivon, F.; Remy, S.; Grelier, G.; Apel, C.; Eydoux, C.; Guillemot, J.C.; Neyts, J.; Delang, L.; Touboul, D.; Roussi, F.; Litaudon, M. Antiviral compounds from Codiaeum peltatum targeted by a multi-informative molecular networks approach. J. Nat. Prod., 2019, 82(2), 330-340.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00800] [PMID: 30681849]
[50]
DellaGreca, M.; Fiorentino, A.; Monaco, P.; Previtera, L.; Zarrelli, A. A new dimeric 9,10-dihydrophenanthrenoid from the rhizome of Juncus acutus. Tetrahedron Lett., 2002, 43(14), 2573-2575.
[http://dx.doi.org/10.1016/S0040-4039(02)00308-8]
[51]
DellaGreca, M.; Fiorentino, A.; Isidori, M.; Lavorgna, M.; Monaco, P.; Previtera, L.; Zarrelli, A. Phenanthrenoids from the wetland Juncus acutus. Phytochemistry, 2002, 60(6), 633-638.
[http://dx.doi.org/10.1016/S0031-9422(02)00152-8] [PMID: 12126711]
[52]
Kilbourn, R.G.; Griffith, O.W. Overproduction of nitric oxide in cytokine-mediated and septic shock. J. Natl. Cancer Inst., 1992, 84(11), 827-831.
[http://dx.doi.org/10.1093/jnci/84.11.827] [PMID: 1375655]
[53]
Vallance, P.; Rees, D.; Moncada, S. Therapeutic potential of NOS inhibitors in septic shock.Nitric Oxide; Springer: Berlin, Heidelberg, 2000, pp. 385-397.
[http://dx.doi.org/10.1007/978-3-642-57077-3_17]
[54]
Dalkara, T.; Endres, M.; Moskowitz, M.A. Mechanisms of NO neurotoxicity. Prog. Brain Res., 1998, 118, 231-239.
[http://dx.doi.org/10.1016/S0079-6123(08)63211-2] [PMID: 9932445]
[55]
Matheis, G.; Sherman, M.P.; Buckberg, G.D.; Haybron, D.M.; Young, H.H.; Ignarro, L.J. Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am. J. Physiol., 1992, 262(2 Pt 2), H616-H620.
[PMID: 1539723]
[56]
Wu, C.C.; Thiemermann, C. Biological control and inhibition of induction of nitric oxide synthase. Methods Enzymol., 1996, 268, 408-420.
[http://dx.doi.org/10.1016/S0076-6879(96)68043-4] [PMID: 8782607]

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