Chemical Constituents and Biological Activities of the Genus Flindersia
(Rutaceae)

Lara Pessanha    Soares    Nascimento; Michel    de Souza    Passos; Thalya Soares    Ribeiro    Nogueira; Mayara    Barreto de Souza    Arantes; Noemi    Oliveira    Monteiro; Samyra    Imad da Silva    Boeno; Antônio    Sérgio Nascimento    Moreira; Milena    Gonçalves Curcino    Vieira; Almir    Ribeiro   de Carvalho Júnior; Raimundo       Braz-Filho; Ivo José    Curcino    Vieira
Abstract

The genus Flindersia comprises 17 species distributed in Australia, New Caledonia, New Guinea, and the Maluku Islands. With a variety of classes of secondary metabolites, including terpenes, alkaloids, lignans, flavonoids, coumarins, among other compounds, to date, the genus has not been widely studied phytochemically, having more value in the timber industry. However, the objective of this review is to gather the necessary information for future research on this genus, for the inclusion of new chemical constituents and biological activities. Thus, we show that the genus Flindersia has more than 160 isolated or identified compounds. In addition, the alkaloids in this genus confer antimalarial activity.
Keywords: Flindersia, secondary metabolites, biological activities, terpenes, alkaloids, phenolic compounds, antifeedant activity
Graphical Abstract

[1] 
Price, J.R. The distribution of alkaloids in the Rutaceae; Chem. Plant Taxonom, 1963, pp. 429-452.
[2] 
Groppo, M.; Pirani, J.R.; Salatino, M.L.; Blanco, S.R.; Kallunki, J.A. Phylogeny of Rutaceae based on two noncoding regions from cpDNA. Am. J. Bot.,  2008, 95(8), 985-1005.
[http://dx.doi.org/10.3732/ajb.2007313] [PMID: 21632420] 
[3] 
Berhow, M.A.; Hasegawa, S.; Kwan, K.; Bennett, R.D. Limonoids and the chemotaxonomy of Citrus and the Rutaceae family. Amer. Chem. Soc.,  2000, 212-229.
[4] 
Mandalari, G.; Bennett, R.N.; Bisignano, G.; Trombetta, D.; Saija, A.; Faulds, C.B.; Gasson, M.J.; Narbad, A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol.,  2007, 103(6), 2056-2064.
[http://dx.doi.org/10.1111/j.1365-2672.2007.03456.x PMID: 18045389] 
[5] 
Cardoso-Lopes, E.M.; Maier, J.A.; da Silva, M.R.; Regasini, L.O.; Simote, S.Y.; Lopes, N.P.; Pirani, J.R. Bolzani, Vda.S.; Young, M.C.M. Alkaloids from stems of Esenbeckia leiocarpa Engl. (Rutaceae) as potential treatment for Alzheimer disease. Molecules,  2010, 15(12), 9205-9213.
[http://dx.doi.org/10.3390/molecules15129205] [PMID: 21160449] 
[6] 
Afonso, L.F. Ontogenia de frutos em Galipeeae (Rutoideae, Rutaceae). M.Sc. Dissertation, Ribeirão Preto Faculty of Philosophy,
  Sciences and Letters: Ribeirão Preto. 2018.
[7] 
Hartley, T.G. A revision of the genus Flindersia (Rutaceae). J. Arnold Arbor.,  1969, 50, 481-526.
[8] 
Hartley, T.G.; Hyland, B.P. Additional notes on the genus Flindersia (Rutaceae). J. Arnold Arbor.,  1982, 56, 243-247.
[9] 
Whiffin, T. Variation and evolution in the genus Flindersia (Rutaceae). I. Review of the genus. Aust. J. Bot.,  1982, 30, 635-643.
[http://dx.doi.org/10.1071/BT9820635] 
[10] 
Scott, K.D.; McIntyre, C.L.; Playford, J. Molecular analyses suggest a need for a significant rearrangement of Rutaceae subfamilies and a minor reassessment of species relationships within Flindersia. Plant Syst. Evol.,  2000, 223, 15-27.
[http://dx.doi.org/10.1007/BF00985324] 
[11] 
Ritchie, E.; Taylor, W.C.; Willcocks, D.V. The chemical constituents of Australian Flindersia species. XII. The constituents of Flindersia xanthoxyla. Aust. J. Chem.,  1960, 13, 426-427.
[http://dx.doi.org/10.1071/CH9600426] 
[12] 
Ritchie, E.; Taylor, W.C.; Vautin, S.T.K. The chemical constituents of Australian Flindersia species. XV. The constituents of Flindersiaacuminata CT White. Aust. J. Chem.,  1961, 14, 469-470.
[http://dx.doi.org/10.1071/CH9610469] 
[13] 
Hollis, A.F.; Prager, R.H.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XIV. The constituents of Flindersia pubescens Bail. and F. schottiana F. Muell. Aust. J. Chem.,  1961, 14, 100-105.
[http://dx.doi.org/10.1071/CH9610100] 
[14] 
Brophy, J.J.; Goldsack, R.J.; Forster, P.I. The leaf oils of the Australian species of Flindersia (Rutaceae). J. Essent. Oil Res.,  2005, 17, 388-395.
[http://dx.doi.org/10.1080/10412905.2005.9698939] 
[15] 
Robertson, L.P.; Hall, C.R.; Forster, P.I.; Carroll, A.R. Alkaloid diversity in the leaves of Australian Flindersia (Rutaceae) species driven by adaptation to aridity. Phytochemistry,  2018, 152, 71-81.
[http://dx.doi.org/10.1016/j.phytochem.2018.04.011] [PMID: 29734038] 
[16] 
Bisignano, G.; Laganà, M.G.; Trombetta, D.; Arena, S.; Nostro, A.; Uccella, N.; Mazzanti, G.; Saija, A. In vitro antibacterial activity of some aliphatic aldehydes from Olea europaea L. FEMS Microbiol. Lett.,  2001, 198(1), 9-13.
[http://dx.doi.org/10.1111/j.1574-6968.2001.tb10611.x] [PMID: 11325546] 
[17] 
Mori, M. n-Hexacosanol and n-octacosanol: Feeding stimulants for larvae of the silkworm, Bombyx mori. J. Insect Physiol.,  1982, 28, 969-973.
[http://dx.doi.org/10.1016/0022-1910(82)90114-7] 
[18] 
Azzouz, M.; Kenel, P.F.; Warter, J-M.; Poindron, P.; Borg, J. Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol. Exp. Neurol.,  1996, 138(2), 189-197.
[http://dx.doi.org/10.1006/exnr.1996.0057] [PMID: 8620917] 
[19] 
Kapitsimadi, C.; Vioryl, S. Effect of a long chain aliphatic alcohol (triacontanol) on growth and yield of different horticultural crops International Symposium on Quality of Fruit and Vegetables: Influence of Pre-and Post-Harvest Factors and Technology,  Greece1995, pp. 237-244.
[20] 
Breen, G.J.W.; Ritchie, E.; Sidwell, W.T.L.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XIX. Triterpenoids from the leaves of F. bourjotiana F. Muell. Aust. J. Chem.,  1966, 19, 455-481.
[http://dx.doi.org/10.1071/CH9660455] 
[21] 
Dewick, P.M. Medicinal Natural Products: A Biosynthetic Approach, 3rd ed; John Wiley & Sons Ltd.: UK, 2009. 
[http://dx.doi.org/10.1002/9780470742761] 
[22] 
Ludwiczuk, A.; Skalicka-Woźniak, K.; Georgiev, M.I. Terpenoids.Pharmacognosy; Badal, S.; Delgoda, R., Eds.; Academic Press: Cambridge, 2017, Vol. 1, pp. 233-266.
[http://dx.doi.org/10.1016/B978-0-12-802104-0.00011-1] 
[23] 
Silva, F.C.; Duarte, L.P.; Vieira Filho, S.A. Celastráceas: fontes de triterpenos pentacíclicos com potencial atividade biológica. Rev. Virtual Quim.,  2014, 6, 1205-1209.
[24] 
Croteau, R.; Kutchan, T.M.; Lewis, N.G. Natural products (secondary metabolites) In: Biochemistry and molecular biology of plants;
  Buchanan, B.; Gruissem, W.; Jones, R., Eds.; , 2000; 24, pp. 1250-1319.
[25] 
Trombetta, D.; Castelli, F.; Sarpietro, M.G.; Venuti, V.; Cristani, M.; Daniele, C.; Saija, A.; Mazzanti, G.; Bisignano, G. Mechanisms of antibacterial action of three monoterpenes. Antimicrob. Agents Chemother.,  2005, 49(6), 2474-2478.
[http://dx.doi.org/10.1128/AAC.49.6.2474-2478.2005 PMID: 15917549] 
[26] 
Crowell, P.L. Prevention and therapy of cancer by dietary monoterpenes. J. Nutr.,  1999, 129(3), 775S-778S.
[http://dx.doi.org/10.1093/jn/129.3.775S] [PMID: 10082788] 
[27] 
Simas, N.K.; Lima, E.D.C.; Conceição, S.D.R.; Kuster, R.M.; Oliveira Filho, A.M.D.; Lage, C.L.S. Natural products to control dengue transmission: Larvicidal activity of Myroxylon balsamum (red oil) and terpenoids and phenylpropanoids. Quim. Nova,  2004, 27, 46-49.
[http://dx.doi.org/10.1590/S0100-40422004000100009] 
[28] 
Santos, M.R.; Moreira, F.V.; Fraga, B.P.; Souza, D.P.D.; Bonjardim, L.R.; Quintans-Junior, L.J. Cardiovascular effects of monoterpenes: A review. Rev. Bras. Farmacogn.,  2011, 21, 764-771.
[http://dx.doi.org/10.1590/S0102-695X2011005000119] 
[29] 
Picker, K.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XXI. An examination of the bark and the leaves of F. laevicarpa. Aust. J. Chem.,  1976, 29, 2023-2036.
[http://dx.doi.org/10.1071/CH9762023] 
[30] 
Safayhi, H.; Sailer, E-R. Anti-inflammatory actions of pentacyclic triterpenes. Planta Med.,  1997, 63(6), 487-493.
[http://dx.doi.org/10.1055/s-2006-957748] [PMID: 9434597] 
[31] 
Dzubak, P.; Hajduch, M.; Vydra, D.; Hustova, A.; Kvasnica, M.; Biedermann, D.; Markova, L.; Urban, M.; Sarek, J. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat. Prod. Rep.,  2006, 23(3), 394-411.
[http://dx.doi.org/10.1039/b515312n] [PMID: 16741586] 
[32] 
Bowden, B.F.; Cleaver, L.; Ndalut, P.K.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XX. An examination of F. pimenteliana. Aust. J. Chem.,  1975, 28, 1393-1395.
[http://dx.doi.org/10.1071/CH9751393] 
[33] 
Moreira, A.S.N. Chemical constituents of Flindersia brayleyana: A contribution to the chemistry of the Rutaceae family. M.Sc. Dissertation, State University of the North Fluminense Darcy
  Ribeiro, Campos dos Goytacazes,. 2001.
[34] 
Binns, S.V.; Halpern, B.; Jughes, G.K.; Ritchie, E. The chemical constituents of Australian Flindersia Species. X. The constituents of F. dissosperma (F. Muell.) domin and its relationship to F. maculosa (Lindl.). F. Muell. Aust. J. Chem.,  1957, 10, 480-483.
[http://dx.doi.org/10.1071/CH9570480] 
[35] 
Brown, R.F.C.; Gilham, P.T.; Hughes, G.K.; Ritchie, E. The chemical constituents of Australian Flindersia species. V. The constituents of Flindersia maculosa Lindl. Aust. J. Chem.,  1954, 7, 181-188.
[http://dx.doi.org/10.1071/CH9540181] 
[36] 
Bosson, J.A.; Rasmussen, M.; Ritchie, E.; Robertson, A.V.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XVII. The structure of Ifflaiamine. Aust. J. Chem.,  1963, 16, 480-490.
[http://dx.doi.org/10.1071/CH9630480] 
[37] 
Bosson, J.A.; Galbraith, M.N.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XVIII. The structure of ifflaionic acid. Aust. J. Chem.,  1963, 16, 491-498.
[http://dx.doi.org/10.1071/CH9630491] 
[38] 
Nimgirawath, S.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XXII. Some extractives of F. brassii. Aust. J. Chem.,  1977, 30, 451-453.
[http://dx.doi.org/10.1071/CH9770451] 
[39] 
Loizou, S.; Lekakis, I.; Chrousos, G.P.; Moutsatsou, P. β-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol. Nutr. Food Res.,  2010, 54(4), 551-558.
[http://dx.doi.org/10.1002/mnfr.200900012] [PMID: 19937850] 
[40] 
Chai, J.W.; Kuppusamy, U.R.; Kanthimathi, M.S. Beta-sitosterol induces apoptosis in MCF-7 cells. Malaysian J. Biochem. Mol. Biol.,  2008, 16, 28-30.
[41] 
Jourdain, C.; Tenca, G.; Deguercy, A.; Troplin, P.; Poelman, D. In-vitro effects of polyphenols from cocoa and β-sitosterol on the growth of human prostate cancer and normal cells. Eur. J. Cancer Prev.,  2006, 15(4), 353-361.
[http://dx.doi.org/10.1097/00008469-200608000-00009] [PMID: 16835506] 
[42] 
Sugano, M.; Morioka, H.; Ikeda, I. A comparison of hypocholesterolemic activity of β-sitosterol and β-sitostanol in rats. J. Nutr.,  1977, 107(11), 2011-2019.
[http://dx.doi.org/10.1093/jn/107.11.2011] [PMID: 908959] 
[43] 
Gupta, R.; Sharma, A.K.; Dobhal, M.P.; Sharma, M.C.; Gupta, R.S. Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia. J. Diabetes,  2011, 3(1), 29-37.
[http://dx.doi.org/10.1111/j.1753-0407.2010.00107.x PMID: 21143769] 
[44] 
Galbraith, M.N.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XIII. The constituents of F. bennettiana F. Muell. Aust. J. Chem.,  1960, 13, 427-429.
[http://dx.doi.org/10.1071/CH9600427] 
[45] 
Breen, G.J.W.; Ritchie, E.; Taylor, W.C. The chemical constituents of Australian Flindersia species. XVI. The constituents of the Wood of Flindersia laevicarpa CT White & Francis. Aust. J. Chem.,  1962, 15, 819-823.
[http://dx.doi.org/10.1071/CH9620819] 
[46] 
Waterman, P.G. Alkaloids of the Rutaceae: Their distribution and systematic significance. Biochem. Syst. Ecol.,  1975, 3, 149-180.
[http://dx.doi.org/10.1016/0305-1978(75)90019-8] 
[47] 
El-Sayed, M.; Verpoorte, R. Catharanthus terpenoid indole alkaloids: Biosynthesis and regulation. Phytochem. Rev.,  2007, 6, 277-305.
[http://dx.doi.org/10.1007/s11101-006-9047-8] 
[48] 
Roy, A. A review on the alkaloids an important therapeutic compound from plants. Int. J. Plant Biol.,  2017, 3, 1-9.
[49] 
Robertson, L.P.; Duffy, S.; Wang, Y.; Wang, D.; Avery, V.M.; Carroll, A.R. Pimentelamines A-C, indole alkaloids isolated from the leaves of the Australian tree Flindersia pimenteliana. J. Nat. Prod.,  2017, 80(12), 3211-3217.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00587] [PMID: 29236492] 
[50] 
Cannon, J.R.; Hughes, G.K.; Price, J.R.; Ritchie, E. The chemical constituents of Australian Flindersia species. IV. The constituents of Flindersia bourjotiana F. Muell. Aust. J. Scientif. Res. A Physic. Sci.,  1952, 5, 420.
[51] 
Anet, F.A.L.; Gilham, P.T.; Gow, P.; Hughes, G.K.; Ritchie, E. The chemical constituents of Australian Flindersia species. III. The Alkaloids of Flindersia collina Bail. Aust. J. Chem.,  1952, 5, 412-419.
[http://dx.doi.org/10.1071/CH9520412] 
[52] 
Brown, R.F.C.; Hobbs, J.J.; Hughes, G.K.; Ritchie, E. The chemical constituents of Australian Flindersia species. VI. The structure and chemisty of Flindersine. Aust. J. Chem.,  1954, 7, 348-377.
[http://dx.doi.org/10.1071/CH9540348] 
[53] 
Tillequin, F.; Koch, M. Trois nouveaux alcaloïdes bis-indoliques de Flindersia fournieri. Phytochemistry,  1979, 18, 1559-1561.
[http://dx.doi.org/10.1016/S0031-9422(00)98496-6] 
[54] 
Tillequin, F.; Koch, M.; Bert, M.; Sevenet, T. Plants of new caledonia. LV. Isoborreverine and borreverine, bis-indolic alkaloids of Flindersia fournieri. J. Nat. Prod.,  1979, 42(1), 92-95.
[http://dx.doi.org/10.1021/np50001a003] [PMID: 27805391] 
[55] 
Fernandez, L.S.; Buchanan, M.S.; Carroll, A.R.; Feng, Y.J.; Quinn, R.J.; Avery, V.M. Flinderoles A.-C: antimalarial bis-indole alkaloids from Flindersia species. Org. Lett.,  2009, 11(2), 329-332.
[http://dx.doi.org/10.1021/ol802506n] [PMID: 19090698] 
[56] 
Ambriz-Pérez, D.L.; Leyva-López, N.; Gutierrez-Grijalva, E.P.; Heredia, J.B. Phenolic compounds: Natural alternative in inflammation treatment. A review. Cogent Food Agric.,  2016, 2, 1-14.
[57] 
Bravo, L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev.,  1998, 56(11), 317-333.
[http://dx.doi.org/10.1111/j.1753-4887.1998.tb01670.x] [PMID: 9838798] 
[58] 
Souza, V.A.; de Nakamura, C.V.; Corrêa, A.G. Anti-chagasic activity of lignans and neolignans. Rev. Virtual Quim.,  2012, 4, 197-207.
[59] 
Lopes, R.M.; Oliveira, T.D.; Nagem, T.J.; Pinto, A.D.S. Flavonóides. Biotecnolog. Cienc. Desenvolv.,  2010, 3, 18-22.
[60] 
de Souza, S.M. Antibacterial activity of natural coumarins and derivatives.. M.Sc. Dissertation, Federal University of Santa Catarina, Santa Catarina,, 2005.
[61] 
Gray, A.I.; Waterman, P.G. Coumarins in the Rutaceae. Phytochemistry,  1978, 17, 845-864.
[http://dx.doi.org/10.1016/S0031-9422(00)88634-3] 
[62] 
Montagner, C. Antifungal, cytotoxic (human tumor cells) and
  hemolytic activities of natural and semi-synthetic coumarins. M.Sc.
  Dissertation, Federal University of Santa Catarina, Santa Catarina,. 2007.
[63] 
Anet, F.A.L.; Hughes, G.K.; Ritchie, E. The chemical constituents of Australian Flindersia species. II. Braylin and Brayleyanin. Aust. J. Chem.,  1949, 2, 608-615.
[http://dx.doi.org/10.1071/CH9490608] 
[64] 
Moreira, A.S.N.; Mathias, L.; Braz-Filho, R.; Schripsema, J.; Vieira, I.J. Two new diprenylated coumarins from Flindersia brayleyana. Nat. Prod. Lett.,  2002, 16(4), 291-295.
[http://dx.doi.org/10.1080/10575630290020668] [PMID: 12168767] 
[65] 
Anet, F.A.L.; Blanks, F.R.; Hughes, G.K. The chemical constituents of Australian Flindersia species. I. Collinin-7-Geranoxy-8-Methoxycoumarin. Australian J. Scient. Res. Phys. Sci.,  1949, 2, 127.
[66] 
Fernandez, L.S. Identification of novel natural product antimalarial compounds. Ph.D. Dissertation, Griffith University, Queensland,, 2010.
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Mini-Reviews in Organic Chemistry

Chemical Constituents and Biological Activities of the Genus Flindersia (Rutaceae)

Abstract

Graphical Abstract
