Journal of Horticultural Research 2014, vol. 22(1): 5-19 DOI: 10.2478/johr-2014-0001 ____________________________________________________________________________________________________________________ THE BIOLOGICAL ACTIVITIES OF TROPONOIDS AND THEIR USE IN AGRICULTURE A REVIEW Marian SANIEWSKI1, Marcin HORBOWICZ2*, Sirichai KANLAYANARAT3 1Research Institute of Horticulture, Konstytucji 3 Maja 1/3, 96-100 Skierniewice, Poland 2Siedlce University of Natural Sciences and Humanities Faculty of Natural Sciences, Department of Plant Physiology and Genetics Prusa 12, 08-110 Siedlce, Poland 3School of Bioresources and Technology, King Mongkut’s University of Technology Thonburi Thungkru, Bangkok 10140, Thailand Received: May 19, 2014; Accepted: June 11, 2014 ABSTRACT Chemical compounds containing the tropone structure (2,4,6-cycloheptatrien-1-one), in their molecule, called troponoids, characterized by a seven-membered ring, are distributed in some plants, bacteria and fungi, although they are relatively rare. ß-Thujaplicin (2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), also known as hinokitiol, is a natural compound found in several plants of the Cupressaceae family. Besides hinokitiol, related compounds were identified in Cupressaceae trees. It has been demonstrated that hinokitiol and its derivatives have various biological effects, such as antibacterial, antifungal, insecticidal, antimalarial, antitumor, anti-ischemic, iron chelating and the inhibitory activity against polyphenol oxidase activity. Activity similar to ß-thujaplicin has tropolone and its derivatives, which are not present nature. Due to the high scientific and practical interest, synthetic ß-thujaplicin and other troponoids have been produced for many years. In this review, the major biological effects of troponoids, mostly ß-thujaplicin and tropolone, on tyrosinase and polyphenol oxidase activity, ethylene production, antibacterial, antifungal and insecticidal activities, and biotransformation of ß-thujaplicin by cultured plant cells are presented. Accumulation of ß-thujaplicin and related troponoids has been shown in cell cultures of Cupressus lusitanica and other species of Cupressaceae. The biosynthetic pathway of the troponoids in plants, bacteria and fungi has been also briefly described. Key words: Cupressaceae, ß-thujaplicin, tropolone, polyphenol oxidase, biosynthesis antibacterial, anti- fungal, insecticidal activity INTRODUCTION & Al-Fahad 2013). Two of the most known tropo- noids, ß-thujaplicin and colchicine, were found in Tropones and tropolones raise increasing inter- plant tissues. Colchicine was first isolated in 1820 est in the past few years due to their potential for use from autumn crocus (meadow saffron, Colchicum in medicine or commerce; approximately 200 such autumnale), although its structure was determined compounds occur in nature (Bentley 2008). Biolog- only in middle of 20th century (King et al. 1952). ical tissues containing the tropolone structure char- ß-Thujaplicin (2-hydroxy-4-isopropyl-2,4,6- acterized by a seven-membered ring and an alpha- cycloheptatrien-1-one), also known as hinokitiol hydroxyl ketone are distributed in plants, bacteria (Fig. 1), is a natural substance found in several and fungi, although they are relatively rare (Cox plants of the Cupressaceae family. The structure of *Corresponding author: e-mail: [email protected] Brought to you by | Florida International University Libraries Authenticated Download Date | 5/28/15 6:34 AM 6 M. Saniewski et al. _____________________________________________________________________________________________________________________ ß-thujaplicin is based on a unique conjugated seven- and related compounds) was documented in the membered ring called a tropolone ring. It has been heartwood of the following tree species: Chamaecy- demonstrated that hinokitiol have a variety of bio- paris obtusa, Ch. lawsoniana, Ch. taiwanensis, logical effects, such as antibacterial, antifungal, an- Ch. thyoides, Cupressus lusitanica, C. arizonica, titumor, anti-ischemic, iron chelating, insecticidal, C. macnabiana, C. macrocarpa, C. torulosa, Juni- antimalarial and inhibitory activity against polyphe- perus chinensis, J. cedrus, J. communis, J. califor- nol oxidase (Zhao 2007; Bentley 2008; Saniewski et nica, J. occidentalis, J. oxycedrus, J. sabina, Calo- al. 2007). Some other hinokitiol-related compounds cedrus decurrens, C. formosana, Platycladus orien- were identified in Cupressaceae trees with similar talis, Thuja occidentalis, T. plicata, T. standishii, or lesser activities to ß-thujaplicin. Details on Thujopsis dolabrata, and Tetraclinis articulata. occurrence of ß-thujaplicin and related compounds Biosynthesis of ß-thujaplicin has been shown including α-thujaplicin, γ-thujaplicin, ß-thujaplicin, in cell cultures of C. lusitanica (Inada et al. 1993; ß-dolabrin, nootkatin and others (Fig. 1) in several Itose & Sakai 1997; Yamaguchi et al. 1999; Cupressaceae trees were reviewed by Haluk and Yamada et al. 2003), C. formosana (Ono et al. Roussel (2000), Chedgy et al. (2007) and Zhao 1998), T. plicata (Haluk & Roussel-Bousta 2003) (2007). Distribution of troponoids (ß-thujaplicin and T. dolabrata var. hondai (Fuji et al. 1995). OMe OH O O O OMe N H OMe tropolone OMe colchicine OH OH HO O O O α-thujaplicin β-thujaplicin γ-thujaplicin (hinokitiol) OH HO O O HO nootkatin β-thujaplicinol Fig. 1. Chemical structures of major troponoids Brought to you by | Florida International University Libraries Authenticated Download Date | 5/28/15 6:34 AM The biological activities of troponoids 7 _____________________________________________________________________________________________________________________ Many factors affect the accumulation of Recently, it has been shown that terpinolene is ß-thujaplicin in cell cultures of Cupressus lusi- a putative intermediate of ß-thujaplicin biosynthesis tanica: elicitors (yeast extract, sodium alginate, and that terpinolene is oxidized into 5-isopropylidene- chitin, methyl jasmonate), Fe2+, Ca2+, G-proteins, 2-methylcyclohex-2-enol (IME). Subsequently, the reactive oxygen species, H2O2, adenosine 3’,5’– IME is oxidized into 1,6-epoxy-4(8)-p-menthen-2-ol cyclic AMP, peroxidase and others. It is believed (EMO), which is also putative intermediate in cultured that crosstalk between jasmonates and ethylene cells of C. lusitanica (Harada et al. 2012) (Fig.2). pathways plays a very important role in biosyn- Activity similar to ß-thujaplicin has tropolone thesis and accumulation of hinokitiol in cell sus- (Fig. 1); however, it is not present in plant tissues pension cultures of C. lusitanica (Zhao & Sakai (Zhao 2007; Bentley 2008, Saniewski et al. 2007; 2003a, b; Zhao et al. 2001, 2003, 2004, 2005, Cox & Al-Fahad 2013). Tropolone and many of its 2006, 2007). derivatives have been synthesized and applied. OPP O OH HO HO O GDP Terpinolene IME EMO β-Thujaplicin (Hinokitiol) Fig. 2. Simplified biosynthetic pathway of ß-thujaplicin (hinokitiol) in Cupressus lusitanica cultured cells (Harada et al. 2012): GDP – geranyl diphosphate, IME – 5-isopropylidene-2-methylcyclohex-2-enol, and EMO: 1,6- epoxy-4(8)-p-menthen-2-ol EFFECTS OF TROPONOIDS ON TYROSINASE A number of tyrosinase inhibitors of both natu- AND POLYPHENOL OXIDASE ACTIVITY ral and synthetic sources that inhibit monophenolase and diphenolase activities have been identified. Enzymatic browning is one of the most studied Among all these inhibitors assayed to date, tropolone processes in fruits, vegetables and other agricultural is one of the most potent (Kim & Uyama 2005). products. This process has an economic significance Tropolone inhibits both mono- and o-dihydroxy- because it influences the storage, processing and phenolase activity of mushroom tyrosinase when quality of agricultural products. The browning is monohydroxyphenols (L-tyrosine) or o-hydroxy- catalysed by the various polyphenol oxidases, such phenols (3,4-dihydroxyphenylanine – DOPA, dopa- as phenoloxidase, phenolase, monophenol oxidase, mine, 4-methyl catechol) were used as the substrates diphenol oxidase and tyrosinase. Polyphenol oxi- (Kahn & Andrawis 1985a). dases are believed to play key physiological roles Tropolone tested in the concentration range of both in preventing insects and microorganisms from 0.3 to 200 µM proved that the higher the tropolone attacking plants and are part of the wound response concentration used, the greater the inhibition of pig- of plants and plant products against insects, micro- ment formation by oxidation of the o-dihydrophenols organisms and bruising. Polyphenol oxidase cataly- investigated. Kahn & Andrawis (1985a) suggest that ses the production of quinones from phenolic com- tropolone and o-dihydroxyphenols compete for bind- pounds, and these quinones undergo reactions with ing to the copper at the active site of the enzyme. amino acids, leading to the production of melanins. o-Dihydroxyphenols can be acted upon by the The melanins form barriers and have antimicrobial tyrosinase as well as by peroxidase and hydrogen properties which prevent the spread of infection or peroxide, leading to the formation of o-quinones bruising in plant tissues (Marshall et al. 2000; Kim which then undergo rapid nonenzymatic conversion & Uyama 2005). to polymeric pigments. Peroxidase can act both on Brought to you by | Florida International University Libraries Authenticated Download Date | 5/28/15 6:34 AM 8 M. Saniewski et al. _____________________________________________________________________________________________________________________