Marmara Pharmaceutical Journal 20: 390-400, 2016 DOI: 10.12991/mpj.20162024853 REVIEW Review on Phytochemistry and Pharmacology of the Genus Licaria (Lauraceae) Wan Mohd Nuzul Hakimi Wan SALLEH, Farediah AHMAD ABSTRACT he genus Licaria (Lauraceae) is a lowering plant genus, comprises 40 species and endemic to Central and South America. Most of the species have been used as traditional medicine. Phytochemicals isolated from Licaria species are lignans, neolignans, alkaloids, lactones, triterpenes, and arylpropanoids. he purpose of this review is to examine in detail from a phytochemical and pharmacological point of view what is reported in the past and current literature obtained from plants belonging to the Licaria genus. Keywords: Licaria, Lauraceae, Phytochemistry, Pharmacology, Neolignans INTRODUCTION Wan Mohd Nuzul Hakimi Wan Salleh, Farediah Ahmad Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia (UTM), 81310 Johor Bahru, Johor, Malaysia Corresponding author Farediah Ahmad E-mail: farediah@kimia.fs.utm.my Tel: +6075534137; Fax: +6075566162 Submitted / Gönderilme: 17.06.2016 Accepted / Kabul: 02.08.2016 390 Revised / Düzeltme: 28.07.2016 he genus Licaria (Lauraceae) is a Neotropical genus consisting of 40 species distributed from southern Florida, Mexico to the south of Brazil and Bolivia. In Brazil, the occurrence of 20 species and two subspecies, mostly in the Amazon region. hese trees have a resilient wood, useful as timber for construction and as firewood (1). he genus evergreen monoecious, hermaphrodite, trees or rarely bushes. It is characterized by the combination of lowers with three 2-locellate stamens, a well-developed cupule, oten with a double margin and alternate and opposite leaves. he fruit is a bay with tepals deciduous and an underlying dome double border (2). Most of Licaria species have ben used in the ethnomedical folk traditions of indigenous Central and South America for various ailments such as indigestion (3), diarrhea (4), stomachache (5), and as stimulant (3). To date, comparative phytochemical data are available for only eleven Licaria species. Several bioactive substances including lignans, neolignans, alkaloids, lactones, triterpenes, essential oils, arylpropanoids, and other components, have been isolated from diferent species of Licaria. Literature reviews show that several of them have been reported with Marmara Pharm J 20: 390-400, 2016 interesting pharmacological activities such as cytotoxicity (6), antibacterial (7), antimalarial (8), anti-leishmanial (4), antioxidant, and antiplatelet inhibitory activities (9). he aim of this review is to examine from phytochemical and pharmacological perspectives the diferent Licaria species for which the extraction, isolation, structural characterization and description of the biological activity of individual compounds are reported in the literature. In addition, the chemical compositions of the essential oils of Licaria species are also reported. A substructure search performed using the SciFinder Scholar database and searches by keywords in PubMed, Medline, and Scopus, indicated that to date 14 species have been cited in this perspective. he discussion on phytochemistry, pharmacology and essential oils compositions of each plant is provided. Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria PHYTOCHEMISTRY AND PHARMACOLOGY A review on the literatures revealed that few phytochemial studies have been carried out on Licaria species prior to the current study. Phytochemical investigations have been conducted on eleven species species of Licaria which are L. aritu Ducke, L. armeniaca (Nees) Kosterm., L. aurea (Huber) Kosterm. L. brasiliensis (Nees) Kosterm., L. canella (Meisn.) Kosterm., L. chrysophylla (Meisn.) Kosterm., L. macrophylla (A.C. Smith) Kosterm., L. mahuba (A. Samp.) Kosterm., L. puchury-major (Mart.) Kosterm., L. rigida Kosterm., and L. triandra (Sw.) Kosterm. he studies have reported the presence of several classes of natural products including lignans, neolignans, alkaloids, lactones, triterpenes, and arylpropanoids. he phytochemical studies of Licaria species are listed in Table 1 and the chemical structures are shown in Figure 1. Table 1. Chemical constituents isolated from the genus Licaria Compounds Species Part L. aritu L. puchury-major L. aritu L. armeniaca Wood Seeds Wood Trunk wood L. armeniaca Trunk wood L. armeniaca L. armeniaca L. puchury-major L. armeniaca Trunk wood Trunk wood Seeds Trunk wood L. armeniaca L. armeniaca Trunk wood Trunk wood L. armeniaca Fruits L. armeniaca Fruits L. armeniaca Fruits L. aurea L. aurea L. aurea L. aurea L. aurea L. chrysophylla Fruits Fruits Fruits Fruits Fruits Bark/fruits calyx Bark/fruits calyx Neolignans Licarin A 1 Licarin B 2 (2S,3S,3aR,5R)-3α-Allyl-5-methoxy-2-(3ʹ,4ʹ-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran 3 (2S,3S,3aR,5R)-3α-Allyl-5,7-dimethoxy-2-(3ʹ,4ʹ-methylenedioxy-phenyl)-3-methyl2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran 4 Armenin A 7 Armenin B 8 (7S,8R, l’S,2’S, 3ʹS)-2’-Acetoxy-l’-allyl-3’,5’-dimethoxy-8-methyl-7-piperonyl-bicyclo [3.2.1]oct-5’- en-4’-one 9 3a-allyl-5-methoxy-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran 12 Dimethoxy-2-(3,4-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran 13 (1S,5R,6S,7R,8R)-8-acetoxy-1-allyl-3,5-dimethoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹ-methylenedioxyphenyl)-4-oxobicyclo[3.2.1]oct-2-ene 17 (1S,5R,6S,7R)-1-Allyl-3-methoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹ-methylenedioxyphenyl)-4,8-dioxobicyclo[3.2.1]oct-2-ene 18 (1S,5R,6S,7R)-1-Allyl-3-methoxy-7-methyl-6-(3ʹ,4ʹ,5ʹ-trimethoxyphenyl)-4,8-dioxobicyclo[3.2.1]oct-2-ene 19 Grandisin 20 de-O-Methylgrandisin 21 dide-O-Methylgrandisin 22 Virolongin A 23 Virolongin B 24 Eusiderin A 27 391 L. chrysophylla 392 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria Marmara Pharm J 20: 390-400, 2016 L. brasiliensis Trunk wood L. brasiliensis Trunk wood L. brasiliensis Trunk wood L. brasiliensis Trunk wood L. brasiliensis Trunk wood L. brasiliensis Trunk wood Chrysophyllin A 40 L. canella L. rigida L. canella L. canella L. rigida L. chrysophylla Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Chrysophyllin B 41 L. chrysophylla Trunk wood Chrysophyllon I-A 42 L. chrysophylla Trunk wood Chrysophyllon I-B 43 L. chrysophylla Trunk wood L. chrysophylla Bark Eusiderin I 51 L. chrysophylla L. chrysophylla L. chrysophylla L. chrysophylla L. chrysophylla L. chrysophylla L. chrysophylla L. chrysophylla Eusiderin J 52 L. chrysophylla Eusiderin K 53 L. chrysophylla Eusiderin L 54 L. chrysophylla Eusiderin M 55 L. chrysophylla Virolongin E 56 L. chrysophylla Virolongin F 57 L. chrysophylla Virolongin G 58 L. chrysophylla Trunk wood Bark Trunk wood Bark Trunk wood Trunk wood Bark Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Bark/fruits calyx Chrysophyllon IV-B 59 Chrysophyllon V1-B 60 Macrophyllin 61 Aurein 67 L. chrysophylla L. chrysophylla L. macrophylla Licaria sp. Bark Bark Trunk wood Wood Eusiderin 68 Licaria sp. Wood L. rigida Trunk wood rel-(7S,8R,1ʹS,4ʹS,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 29 rel-(7S,8R,1ʹS,4ʹR,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 30 rel-(7S,8R,1ʹS,5ʹS,6ʹS)-6-Acetoxy-3ʹ-hydroxy-3,5ʹ-dimethoxy-4,5-methylenedioxy-4ʹ-oxo-Δ1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 31 rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6-Acetoxy-3,4,5,3ʹ,5ʹ-pentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 32 rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 33 rel-(7S,8R,1ʹS,4ʹR,5ʹS,6ʹS)-6ʹ-Acetoxy-4ʹ-hydroxy-3,3ʹ,5ʹ-trimethoxy-4,5-methylenedioxy-Δ1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 34 Canellin A 35 Canellin B 36 Canellin C 37 Chrysophyllon II-A 44 Chrysophyllon II-B 45 Chrysophyllon III-A 46 Chrysophyllon III-B 47 Marmara Pharm J 20: 390-400, 2016 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria (7S,8S)-∆8ʹ-2ʹ,6ʹ-Dimethoxy-3,4,-methylenedioxy-7.O.3ʹ,8.4ʹ,1ʹ.O.7ʹ-neolignan 75 Ferrearin B 76 Ferrearin C 77 rel-(7S,8S,1ʹR,2ʹS)-2ʹ-Hydroxy-3,4-dimethoxy-3ʹ-oxo-∆4ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 78 Ferrearin G 79 Oxaguianin 80 rel-(7S,8S,1ʹR,5ʹR)-5ʹ-Methoxy-3,4-methylenedioxy-4ʹ-oxo-∆2ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 81 3ʹ-Methoxyburchellin 82 Eusiderin B 93 Triandrin A 94 Triandrin B 95 Burchellin 96 Lignans Magnolin 11 Alkaloids tri-O-Methylmoschatoline 10 Bracteoline 14 O-Methylbracteoline 15 α-Dehydroreticuline 16 Reticuline 83 Orientaline 84 Coclaurine 85 N-methylcoclaurine 86 Norjuziphine 87 Norisoboldine 88 Isoboldine 89 Glaziovine 90 Reticuline N-oxide [91 N-Me (S)] Reticuline N-oxide [92 N-Me (R)] Lactones (-)-Dihydromahubanolide B 65 (-)-iso-Dihydromahubanolide B 66 Miscellaneous compounds Sitosterol 5 L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. rigida L. triandra L. triandra L. triandra Seeds Seeds Seeds Seeds Seeds Seeds Seeds Seeds Trunk wood Seeds Seeds Seeds L. armeniaca Trunk wood L. armeniaca L. armeniaca L. armeniaca L. armeniaca L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major Trunk wood Trunk wood Trunk wood Trunk wood Seeds Seeds Seeds Seeds Seeds Seeds Seeds Seeds Seeds Seeds L. mahuba L. mahuba Trunk wood Trunk wood Dillapiole 38 Elemicin 39 2,3,4,5-Tetramethoxyallylbenzene 48 2,3,4,5-Tetramethoxycinnamyl alcohol 49 2,3,4,5-Tetramethoxycinnamaldehyde 50 Borneol 62 Elemol 63 L. armeniaca L. armeniaca L. canella L. macrophylla L. puchury-major L. armeniaca L. armeniaca L. canella L. canella L. chrysophylla L. chrysophylla L. chrysophylla L. macrophylla L. macrophylla Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood Nerolidol 64 L. macrophylla Trunk wood Eugenol 69 Safrole 70 Syringic aldehyde 71 3,4-Methylenedioxycinnamaldehyde 72 3,4-Methylenedioxycinnamyl alcohol 73 L. puchury-major L. puchury-major L. puchury-major L. puchury-major L. puchury-major Trunk wood Trunk wood Trunk wood Trunk wood Trunk wood 6,7-Dimethoxycoumarin 6 393 394 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria L. aritu Ducke L. aritu is an arboreous Lauraceae species which occurs along the Manaus-Itacoatiara road, Amazonas State. he only literature report refers to the isolation from the benzene extract of the wood have characterize licarin A 1 and B 2 (10). L. armeniaca (Nees) Kosterm. L. armeniaca is a tree up to 7 m, widely distributed in the Amazonian rainforest, Brazil. Four studies have been reported from this species. he first report was published in 1978 by Aiba and co-workers (11). hese authors isolated two novel benzofuranoid neolignans, namely (2S,3S,3aR,5R)3α-allyl-5-methoxy-2-(3ʹ,4ʹ-methylenedioxyphenyl)3-methyl-2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran 3 and (2S,3S,3aR,5R)-3α-allyl-5,7-dimethoxy-2(3ʹ,4ʹ-methylenedioxy-phenyl)-3-methyl-2,3,3a,4,5,6hexahydro-6-oxo-benzofuran 4, together with sitosterol 5,6,7-dimethoxycoumarin 6, armenin A 7, and armenin B 8 from the benzene extract of trunk wood. Purification of the benzene/ethanol extract of the trunk wood by Alegrio et al. (12) have reported to have a novel neolignan (7S,8R, l’S,2’S, 3ʹS)-2’-acetoxy-l’-allyl-3’,5’-dimethoxy-8methyl-7-piperonyl-bicyclo [3.2.1]-oct-5’-en-4’-one 9, including sitosterol 5,6,7-dimethoxycoumarin 6, tri-Omethylmoschatoline 10 and magnolin 11. In addition, Abdel-Hafiz and co-workers (13) have successfully isolated two neolignans, 3a-allyl-5-methoxy-3-methyl-2,3,3a,4,5,6hexahydro-6-oxobenzofuran 12 and dimethoxy-2-(3,4methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro6-oxobenzofuran 13, including three alkaloids, bracteoline 14, O-methylbracteoline 15 and α-dehydroreticuline 16. Barbosa-Filho and co-workers (14) have studied on the fruits part. he isolation on ethanol/water extract have found three novel neolignans (1S,5R,6S,7R,8R)-8-acetoxy1-allyl-3,5-dimethoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹmethylenedioxyphenyl)-4-oxobicyclo[3.2.1]oct-2-ene 17, (1S,5R,6S,7R)-1-allyl-3-methoxy-7-methyl-6-(3ʹ-methoxy4ʹ,5ʹ-methylenedioxyphenyl)-4,8-dioxobicyclo[3.2.1]oct2-ene 18, and (1S,5R,6S,7R)-1-allyl-3-methoxy-7-methyl6-(3ʹ,4ʹ,5ʹ-trimethoxyphenyl)-4,8-dioxobicyclo[3.2.1] oct-2-ene 19. L. aurea (Huber) Kosterm. L. aurea is a tree widely distributed in the Amazonian rainforest, Brazil. he ethanolic fruit extract of L. aurea have found to contain the diaryltetrahydrofuran type neolignans, grandisin 20, de-O-methylgrandisin 21 and Marmara Pharm J 20: 390-400, 2016 dide-O-methylgrandisin 22, as well as virolongin A 23 and virolongin B 24, as reported by Barbosa-Filho and co-workers (15). Bezerra and co-workers (16) also successfully isolated grandisin 20 from this species. hree years later, Marques et al. (17) were studied on wood part and successfully identified as aurein A-B 25-26, eusiderin A 27, virolongin B 24 and virolongin C 28. L. brasiliensis (Nees) Kosterm. L. brasiliensis is a tree popularly known as ‘louro capitiu’, grows wild in the Forest Reserve of Jari, Municipality of Almerim, Brazil (18). Phytochemical studies on the hexane extract of the trunk wood of this species have led to the isolation of six new bicycle[3.2.1]octanoid neolignans, identified as rel-(7S,8R,1ʹS,4ʹS,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹpentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 29, rel-(7S,8R,1ʹS,4ʹR,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹpentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 30, rel-(7S,8R,1ʹS,5ʹS,6ʹS)-6-acetoxy-3ʹ-hydroxy-3,5ʹdimethoxy-4,5-methylenedioxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ8.1ʹ,7.5ʹ-neolignan31,rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6-acetoxy-3,4,5,3ʹ,5ʹpentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 32, rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6ʹ-hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 33, and rel-(7S,8R,1ʹS,4ʹR,5ʹS,6ʹS)-6ʹ-acetoxy-4ʹ-hydroxy3,3ʹ,5ʹ-trimethoxy-4,5-methylenedioxy-Δ-1,3,5,2ʹ,8ʹ8.1ʹ,7.5ʹ-neolignan 34 (18). L. canella (Meisn.) Kosterm. L. canella is a botanical species popularly known as ‘louropirarucu’. Within the ethnic group Tacana of the Amazonian region, this species has the same name and use as Aniba canelilla, probably due to their aromatic barks. he barks of both species have ethnopharmacological uses to alleviate abdominal pain, intestinal cramps or discomfort, without diarrhea (8). he ethanol extract of the bark of this species showed activity in vitro against chloroquine sensitive Plasmodium falciparum (IC50 value of 3.8 μg/mL) and also resistant strains (IC50 value of 3.2 μg/mL). he extract of the stem demonstrated low activity against human myeloma cell line, RPMI 8226 cancer cells (8). Giesbrecht and co-workers (19) have reported the benzene/ethanol extract of the trunk wood to have three neolignans, canellin A 35, B 36 and C 37, as well as dillapiole 38, elemicin 39 and sitosterol 5. L. chrysophylla (Meisn.) Kosterm. L. chrysophylla is a tree growing in Amazonian rainforest, Marmara Pharm J 20: 390-400, 2016 Brazil. he first and up to now, four studies have been reported from this species. Ferreira and co-workers (20) have isolated chrysophyllin A 40 and B 41 from petroleum extract of the trunk wood. Both compounds were also found from the same species, reported by Lopes et al. (21). hey also managed to obtain chrysophyllon I-A 42, chrysophyllon I-B 43, chrysophyllon II-A 44, chrysophyllon II-B 45, chrysophyllon III-A 46, chrysophyllon III-B 47, 2,3,4,5-tetramethoxyallylbenzene 48, 2,3,4,5-tetramethoxycinnamyl alcohol 49 and 2,3,4,5-tetramethoxycinnamaldehyde 50 form the petroleum extract of trunk wood. Furthermore, Silva and co-workers (22) have reported on the other parts of this species which are from the bark and fruits calyx ethanolic extract. hey found five new benzodioxane neolignans, eusiderin I-M 51-55, three new β-aryloxy-arylpropane type neolignan, virolongin E-G 56-58, together with known compounds, eusiderin A 27 and virolongin B 24. In addition, Bezerra et al. (16) have studied on the bark extract of this species and successfully isolated chrysophyllon IV-B 59, chrysophyllon V1-B 60, chrysophyllon I-B 43, chrysophyllon II-A 44, chrysophyllon II-B 45, chrysophyllon III-B 47. hey also found that the isolated compound have strong inhibition of supercoiled DNA relaxation induced by topo II-α at a concentration of 100 μM. hese results indicate that no obvious correlation can be derived between the structure of these compounds and the inhibitory activity of DNA relaxation by DNA topoisomerase II. L. macrophylla (A.C. Smith) Kosterm. L. macrophylla is a tree which grows in the Amazon region, Brazil (23). Only one study has been reported in the literature about this plant in 1974, when Franca and coworkers (23) described the isolation and characterization of a novel neolignan, macrophyllin 61 from the trunk wood extracts. Besides, they also managed to get sitosterol 5, borneol 62, elemol 63, and nerolidol 64. L. mahuba (A. Samp.) Kosterm. L. mahuba, an Amazonian Lauraceae has been reported to have (-)-dihydromahubanolide B 65 and (-)-isodihydromahubanolide B 66. Synthesis of both compounds was achieved starting from (-)-methyl 5-hydroxymethyl2,2-dimethyl-1,3-dioxolane-4-carboxylate which was readily available from L-(+)-tartaric acid, as published by Tanaka and Yamashita (24). Gottlieb and co-workers (25) also Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria 395 reported the phytochemical study from the wood of a Licaria sp. hey were successfully identified two neolignans, namely aurein 67 and eusiderin 68. L. puchury-major (Mart.) Kosterm. L. puchury-major is populary known in Brazil as ‘puchuri’ or ‘pixuri’. heir seeds are used in folk medicine for stomach and intestinal ailments and also as a calmative in adults and children to treat insomnia, nervousness and irritability (26). he first phytochemical study of this species appeared in the literature in 1973 when Leao da Silva and co-workers (27) isolated and structurally characterized sitosterol 5, eugenol 69, safrole 70, syringic aldehyde 71, 3,4-methylenedioxycinnamaldehyde 72 and 3,4-methylenedioxycinnamyl alcohol 73 from trunk wood extract. In addition, Uchiyama and co-workers (28) have reported that the EtOH extract of the seeds of L. puchury-major showed the growth inhibitory activity against human leukemia Jurkat cells (53.3% inhibition at 30 μg/mL). Besides, acetone fraction was found to be the most active (82.7% inhibition at 30 μg/mL) and induced early apoptosis at 30 μg/mL within 24 h against Jurkat cells. Bioassay-guided fractionation of the ethanol extracts led to the isolation of one phenylpropanoid and ten neolignans. hey were identified as apiole 74, (7S,8S)-∆8ʹ-2ʹ,6ʹ-dimethoxy-3,4,-methylenedioxy7.O.3ʹ,8.4ʹ,1ʹ.O.7ʹ-neolignan 75, ferrearin B 76, ferrearin C 77, licarin A 1, rel-(7S,8S,1ʹR,2ʹS)-2ʹ-hydroxy-3,4dimethoxy-3ʹ-oxo-∆4ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 78, ferrearin G 79, oxaguianin 80, rel-(7S,8S,1ʹR,5ʹR)-5ʹ-methoxy-3,4methylenedioxy-4ʹ-oxo-∆2ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 81, armenin B 8, and 3ʹ-methoxyburchellin 82. he cytotoxic activity of isolated compounds against Jurkat was tested by MTT assay and found that compounds 76, 77, 78 and 79 having furanocyclohexenone structure with hemiacetal in the molecule showed cytotoxic activity at 10 µM. hese four neolignans induced early apoptosis at 10 µM within 24 h, while compound 75 also induced apoptosis at 100 µM within 48 h. Studies on this species was continued by Ohsaki and co-workers (6) and successfully isolated ten alkaloids from the seeds extract. hey were identified as reticuline 83, orientaline 84, coclaurine 85, N-methylcoclaurine 86, norjuziphine 87, norisoboldine 88, isoboldine 89, glaziovine 90 and reticuline N-oxide [91 N-Me (S); 92 N-Me (R)]. he cytotoxicity of the obtained compounds was evaluated against vincristine-sensitive and -resistant P388 cells in the presence of P388/VCR(+) or the absence of P388/VCR(-) of low levels of vincristine. Norjuziphine 87, norisoboldine 88, and isoboldine 89 exhibited potent cytotoxic activity in the presence of vincristine P388/VCR(+). 396 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria 1 R1 = R2 = OCH2O 2 R1 = OCH3 ; R2 = OH 3 R=H 4 R = OCH3 9 10 14 R = H 15 R = OCH3 16 23 24 28 56 57 58 38 6 18 R1 = R2 = OCH2O 19 R1 = R2 = OCH3 25 R1 = OCH3 ; R2 = OCH3 26 R1 = R2 = OCH2O 27 51 52 53 54 55 93 13 20 R1 = R2 = CH3 21 R1 = H ; R2 = CH3 22 R1 = R2 = H trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CH2CH=CH2 trans, R1 = R2 = CH2 ; R3 = OCH3 ; R4 = CH3 ; X = CH2CH=CH2 cis, R1 = H ; R2 = H ; R3 = H ; R4 = H ; X = CH2CH=CH2 trans, R1 = R4 = CH3 ; R2 = H ; R3 = OCH3 ; X = CH2CH=CH2 trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CHO trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CH=CHCH2OH trans, R1 = R2 = CH2 ; R3 = H ; R4 = CH3 ; X = CH2CH=CH2 32 R1 = OAc ; R2 = H 33 R1 = OH ; R2 = H 39 7 R=H 8 R = OCH3 12 17 31 29 R1 = OH ; R2 = H 30 R1 = H ; R2 = OH 5 11 R1 = R2 = CH3 ; X = CH=CHCH3 R1 = R2 = CH3 ; X = CH2CH=CH2 R1 - R2 = CH3 ; X = CH2CH=CH2 R1 = R2 = CH3 ; X = CH=CHCH2OH R1 = R2 = CH3 ; X = CH=CHCHO R1 = R2 = CH3 ; X = CHO 37 Marmara Pharm J 20: 390-400, 2016 40 R1 = R2 = OCH2O 41 R1 = R2 = OCH3 34 35 R1 = OCH3 ; R2 = OCH3 ; R3 = H 36 R1 = R2 = OCH2O ; R3 = OCH3 42 R1 = R2 = OCH2O 43 R1 = R2 = OCH3 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria Marmara Pharm J 20: 390-400, 2016 44 R1 = R2 = OCH2O 45 R1 = R2 = OCH3 46 R1 = R2 = OCH2O 47 R1 = R2 = OCH3 59 60 63 72 71 77 R = H 79 R = OCH3 76 82 R = OCH3 96 R = H 90 83 R1 = OH ; R2 = OCH3 84 R1 = OCH3 ; R2 = OH 91 N-CH3 = (S) 92 N-CH3 = (R) 49 50 61 62 67 65 R1 = H ; R2 = C15H31 66 R1 = C15H31 ; R2 = H 64 69 R1 = OCH3 ; R2 = OH 70 R1 = R2 = OCH2O 48 68 73 78 74 75 81 80 85 R = H 86 R = CH3 94 Figure 1. Chemical structures of the compounds isolated from the genus Licaria 88 R = H 89 R = CH3 87 95 397 398 Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria Marmara Pharm J 20: 390-400, 2016 Table 2. Essential oils compositions from the genus Licaria Species Locality Parts/Major components L. canella Brazil Leaves: Benzyl Benzoate (69.7-73.0%), α-copaene (4.5-4.9%), α-phellandrene (3.3-4.2%), α-pinene (3.0-3.5%) (4) L. excelsa Costa Rica Leaves: α-Pinene (42.9%), β-pinene (22.0%) (31) L. macrophylla Brazil Wood: Elemol (25.0%), nerolidol (5.0%), borneol (3.0%) (27) L. martiniana Brazil Leaves: β-Caryophyllene (41.7%), β-selinene (7.9%), isovalerate linalool (5.9%), linalool (5.3%) (9) Brazil Stems: β-Caryophyllene (21.4%), spathulenol (11.5%), linalool (6.5%), α-cadinol (5.9%), γ-cadinene (5.7%) (9) L. puchury-major L. salicifolia L. triandra Brazil Twigs: Eugenol (61.0%), safrole (20.1%), eucalyptol (10.8%), α-terpineol (6.8%) (32) Brazil Leaves: Eucalyptol (47.6%), safrole (21.7%), α-terpineol (11.7%) (32) Brazil Seeds: Safrole (51.3%), eugenol (3.3%), methyl eugenol (2.9%) (33) Brazil Seeds: Safrole (36.1%), 1,8-cineole (21.1%), limonene (12.2%), α-terpineol (10.7%) (34) Brazil Seeds: Safrole (58.4%), dodecanoic acid (13.7%), α-terpineol (8.4%) (5) France Leaves: α-Phellandrene (17.2-22.0%), α-santalene (0.8-20.3%), p-cymene (1.5-17.4%), β-santalene (0.2-7.0%) (35) France Bark: p-Cymene (10.1-13.0%), α-phellandrene (5.3-8.1%), 7-epi-α-santalene (7.3-7.6%), α-cadinol (4.5-6.5%), caryophyllene oxide (4.3-6.2%) (35) France Fruits: α-Cantalene (2.0-19.0%), p-cymene (11.0-13.5%), α-phellandrene (5.8-13.0%), β-santalene (0.7-9.2%) (36) Cuba Leaves: Selin-11-en-4α-ol (15.1%), β-pinene (10.6%), β-caryophyllene (9.5%), spathulenol (5.6%) (29) Cuba Leaves: β-Eudesmol (11.4%), caryophyllene oxide (3.0%) (29) Costa Rica Leaves: α-Pinene (40.9%), β-pinene (28.5%) (E)-caryophyllene (6.5%) (30) L. rigida Kosterm. L. rigida, collected at the Ducke Forest Reserve, near Manaus, Amzonas State, have been investigated by Fo et al. (7). hey managed to isolate three neolignans from the trunk wood extract, namely eusiderin 68, eusiderin B 93, canellin A 35 and canellin C 37. L. triandra (Sw.) Kosterm. L. triandra is a tree 7-16 m high. It is frequent in woodlands on limestone or shale, 100-1000 m, lowering in SeptemberNovember, fructifying in January-September. It grows wild in Florida and West Indies southward to Martinique (29). he leaves are used locally as folk medicine such as against indigestion, stomachache and as stimulant (3). Phytochemical investigation from the seeds of this species have aforded two new neolignans, identified as triandrin A-B 94-95 (18) as well as a known benzofuranoid neolignan, burchellin 96 as reported by Castro and Ulate (30). Literatures revealed that few essential oils studies have been carried out on Licaria species. he chemical compositions of the essential oils of Licaria species have been conducted on seven species, which are L. canella (4), L. excelsa (31), L. macrophylla (27), L. martiniana (9), L. puchury-major (5,32,33,34), L. salicifolia (35), and L. triandra (29,31,36). he major components of the essential oil compositions from Licaria species are tabulated in Table 2. Monoterpenes hydrocarbon was found as the major group components, in the essential oil of L. triandra (Cuba: 42.9%; Costa Rica: 77.7%) (29,31) and L. excelsa (85.7%) (31). Meanwhile, oxygenated monoterpenes and benzenoids were found from the essential oil of L. puchury-major (seeds: 34.3%) (5) and L. canella (leaves: 71.3-74.9%) (4), respectively. In addition, sesquiterpene hydrocarbons were found from the essential oil of L. martiniana (47.0-65.8%) (9). Benzyl benzoate, eugenol, and safrole were the major components identified with more than 50% in the essential oils of Licaria species. Benzyl benzoate was found in 69.7-73.0% from the leaves oil of L. canella (4). Other studies have demonstrated that benzyl benzoate is efective at denaturing dust miteallergen (37) and can eradicates mites and reduce their populations (38). In addition, eugenol presented 61.0% from the twigs oil of L. Salleh and Ahmad Phytochemistry and Pharmacology of the Genus Licaria Marmara Pharm J 20: 390-400, 2016 puchury-major (32). It has been shown in the pharmacological studies that eugenol demonstrated anesthetic, hypothermic, muscle-relaxant, antistress efect and anticonvulsant activities (39,40). Besides, the seeds oil from the same species has successfully found safrole in 51.3% (33) and 58.4% (5). Studies have revealed the genotoxic (41) and carcinogenic (42) potentials of safrole. he study of Taiwanese oral cancer patients suggests that safrole may form stable safrole-DNA adducts in human oral tissues following betel quid chewing, which may contribute to oral carcinogenesis (43). he in vitro antibacterial activity of the essential oil of L. triandra was studied against five bacteria strains (Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis and Escherichia coli) using the disc difusion method. he essential oil showed weak activity against the bacteria tested (29). Palazzo and co-workers (31) have evaluated in vitro cytotoxicity activity of the essential oils of L. excelsa and L. triandra against human breast adenocarcinoma cells (MDA-MB-231/MDA-MB-231) and human breast ductal carcinoma cells (Hs 578T). he essential oil of L. triandra was found weak activity with 25% kill at 100 µg/mL, while L. excelsa oil found to be inactive. he evaluation of the antileishmanial activity of the essential oil of L. canella indicated moderate activity against Leishmania amazonensis with IC50 value of 19 μg/mL. Meanwhile, the essential oil displayed low cytotoxicity against Artemia salina with LC50 value of 5.25 μg/ mL (4). Besides, the essential oils of L. martiniana showed Licaria (Lauraceae) Türlerinin Fitokimyasal ve Farmakolojik Özellikleri Üzerine Bir Derleme ÖZ Licaria (Lauraceae) çiçekli bir bitki olup 40 cinsi vardır ve bu cinslerin bazıları Orta ve Güney Amerika’ya ait endemik bitkilerdir. Licaria (Lauraceae) türlerinin çoğu geleneksel halk weak antioxidant (DPPH >1000 μg/mL) and antiplatelet inhibitory activities (leaves 4.2%; stems 36.9%) at quantitative spectrometric assays (9). CONCLUSION In this review, we summarized the secondary metabolites isolated from the genus Licaria and their pharmacological properties. Most of the species produced lignans and neolignans. Apart from that, further phytochemical studies need to be carried out in the near future to provide a more detailed pattern of the natural constituents and of the biologically active principles in extracts. As a conclusion, it is evident that the genus Licaria comprises therapeutically promising and valuable plants, some of which are used in the traditional medicine of indigenous populations. Meanwhile, there are only few studies describing their pharmacological properties, this genus merits more attention in the on-going search for new bioactive compounds. ACKNOWLEDGMENTS he authors thank to Research University Grant (GUPQJ130000.2526.03H93) for financial support and the Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia (UTM) for research facilities. ilacı olarak kullanılmaktadır. Licaria türlerinden izole edilen fitokimyasallar; lignanlar, neolignanlar, alkaloidler, laktonlar, triterpenler ve arilpropanoit’lerdir. Bu derlemenin amacı, Licaria türlerine ait bitkileri konu alan hem eski hem de güncel literatürün bitkilerin farmakolojik ve fitokimyasal özellikleri açısından ayrıntılı olarak incelenmesidir. Anahtar kelimeler: Licaria, Lauraceace, Fitokimya, Farmakoloji, Neolignanlar REFERENCES 1. 2. 3. 4. Kurz H. Fortplanzungsbiologie einiger Gattungen neotropischer Lauraceen und Revision der Gattung Licaria. Dissertation zur Erlangung der Doktorwürde des Fachbereichs Biologie. Universität Hamburg, Hamburg, 1983. van der Werf H. Nine new species of Licaria (Lauraceae) from Tropical America. 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