CC BY-NC-ND 4.0 · Planta Medica International Open 2019; 6(02): e36-e40
DOI: 10.1055/a-0977-4418
Original Papers
Eigentümer und Copyright ©Georg Thieme Verlag KG 2019

Cytotoxicity and Antibacterial Potential of Halogenated Chamigrenes from Malaysian Red Alga, Laurencia majuscula

Takashi Kamada
1   Laboratory of Natural Products Chemistry, Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, 88450 Kota Kinabalu, Sabah, Malaysia
2   Laboratory of Natural Products Chemistry, Department of Materials and Life Science, Faculty of Science and Technology, Shizuoka Institute of Science and Technology, Fukuroi, Shizuoka 437-8555, Japan
,
Chin-Soon Phan
1   Laboratory of Natural Products Chemistry, Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, 88450 Kota Kinabalu, Sabah, Malaysia
,
Tatsufumi Okino
3   Graduate School of Environmental Science, Faculty of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan
,
Charles Santhanaraju Vairappan
1   Laboratory of Natural Products Chemistry, Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, 88450 Kota Kinabalu, Sabah, Malaysia
› Author Affiliations
Further Information

Correspondence

Prof. Dr. Charles Santhanaraju Vairappan
Laboratory of Natural Products Chemistry
Institute for Tropical Biology and Conservation
Universiti Malaysia Sabah
Jalan UMS
88400 Kota Kinabalu
Sabah
Malaysia
Phone: +60/88/320 000 ext. 2384   
Fax: +60 88 320 291   

Publication History

received 05 March 2019
revised 08 July 2019

accepted 15 July 2019

Publication Date:
21 August 2019 (online)

 

Abstract

Red algae of the genus Laurencia have been known to produce a wide array of bioactive secondary metabolites. Here, we report the isolation of two new halogenated chamigrenes, lauremantanones A (1) and B (2), along with seven known compounds, dendroidiol (3), (+)-elatol (4), cartilagineol (5), obtusol (6), (+)-laurencenone B (7), 2-chloro-3-hydroxy-α-chamigren-9-one (8), and puertitol A (9), from a population of Laurencia majuscula (Harvey) Lucas from Mantanani Island (North Borneo). The structures of the two new metabolites were determined based on spectroscopic data (IR, 1D and 2D NMR, and MS). Compounds isolated from this alga exhibited potent cytotoxic (HeLa, MCF-7, P-388) and antibacterial (against antibiotic-resistant clinical bacteria) activities. The major metabolite of this population has significant importance in the geographical distribution of this species globally.


#

Introduction

Red algae of the genus Laurencia are known to produce an array of diverse halogenated secondary metabolites represented as terpenoid, alkaloid and C15-acetogenin chemical skeletons [1] [2] [3] [4]. Presence and quantity of the major halogenated metabolites within Laurencia populations often vary with their species and geographical distribution [5] [6] [7] [8] [9]. Halogenated compounds have also been shown to exhibit various biological activities with pharmaceutical importance, such as antibacterial [7], cytotoxic [10], and insect repellent activities [11]. As part of our ongoing effort to document the diversity of halogenated secondary metabolites, we collected a population of Laurencia majuscula from the coastal waters of North Borneo (Mantanani Island), which led to the isolation of two new sesquiterpenoids, lauremantanones A (1) and B (2), along with seven known compounds, dendroidiol (3) [12], (+)-elatol (4) [13], cartilagineol (5) [14] [15] [16], obtusol (6) [15] [16] [17], (+)-laurencenone B (7) [18] [19], 2-chloro-3-hydroxy-α-chamigren-9-one (8) [13] [20], and puertitol A (9) [21] ([Fig. 1]). Herein, we describe the isolation, structural elucidation, cytotoxicity, and antibacterial activities of these compounds.

Zoom Image
Fig. 1 Structures of sesquiterpenoids 1–9 from L. majuscula.

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Results and Discussion

Compound 1 was isolated as colorless oil, [α]D 28 +22.3 (c 1.0, CHCl3). The molecular formula was established as C15H21ClO2 by the HRESIMS [M + H]+ ion at m/z 269.1305 (calcd. for C15H22ClO2, 269.1303) and it accounted for 5 degrees of unsaturation. Its IR absorption was seen at 3 420 and 1 650 cm−1, indicating the presence of hydroxyl (-OH) and α,β unsaturated carbonyl (C=O) functionalities. The 13C NMR revealed the presence of 15 signals whose multiplicities were attributed by DEPT-135 and HSQC spectra to three methyls, five methylenes, including an oxygenated methylene, a trisubstituted, and a tetrasubstituted olefins, two quaternary carbons, and a carbonyl carbon. These signals accounted for three degrees of unsaturation, implying 1 possesses a bicyclic system. The NMR data ([Table 1]) of 1 closely resembled that of 7 except for the replacement of a vinyl methyl at C-14 in 7 by a vinyl carbinol moiety in 1 [[18] [19] [22]. The presence of a carbinol unit was further confirmed by its deshielded chemical shifts at C-14 (δ C 64.0; δ H 4.24) [23], IR absorption at 3 420 cm−1, and HRESIMS spectrum.

Table 1 13C and 1H NMR (150 and 600 MHz) data of 1 and 2 (CDCl3, δ in ppm, J in Hz).

1

2

No.

δ C

δ H

δ C

δ H

1

36.2

2.55 d (17.9)

35.4

2.24 d (6.2)

2.26 d (17.9)

2.23 d (11.0)

2

126.4

68.4

4.28 dd (11.0, 6.2)

3

130.4

70.6

4

30.8

2.17 dd (17.2, 5.5)

36.9

1.93–1.95 m

2.00–203 m

1.78–1.81 m

5

31.2

1.92 td (12.4, 5.5)

23.8

1.97–1.99 m

1.76 ddt (12.4, 4.8, 2.1)

1.78–1.81 m

6

46.2

47.5

7

171.1

168.7

8

124.1

6.32 s

124.5

6.18 s

9

199.3

199.1

10

49.8

2.64 d (17.2)

50.6

2.41 d (19.3)

2.10 d (17.2)

2.36 d (19.3)

11

41.3

41.6

12*

25.2

1.06 s

28.1

1.16 s

13*

24.6

0.96 s

27.9

1.13 s

14

64.0

4.24 s

63.9

4.46 d (16.5)

4.42 d (16.5)

15

20.4

1.79 s

29.3

1.36 s

*Assignments may be reversed

The 1H-1H COSY (Fig. 1S, Supporting Information) correlation between H2–4 and H2–5, together with the HMBC (Fig. 1S, Supporting Information) correlations from H3–12, 13 to C-6, 10, 11, from H3–15 to C-2, 3, 4, from H2–14 to C-6, 7 , 8, from H2–1 to C-2, 5, 6, from H2–10 to C-9, and from H-8 to C-10 were enough to establish the planar structure of an α-chamigrane-type sesquiterpenoid for 1. The relative configuration at C-6 was assigned S*, identical to that of (+)-7, based on a chemical shift (δ C 46.4) and the optical rotation [α]D 25 +39.4 (c 0.2, CHCl3) as well as a biogenetic pathway given the fact that both compounds were isolated from the same specimen. (Fig. 2S–7S)

Compound 2 was isolated as colorless oil, [α]D 28–35.0 (c 0.5, CHCl3). The molecular formula was determined as C15H23ClO3 through the HRESIMS [M + H]+ ion at m/z 287.1412 (calcd. for C15H24ClO3, 287.1409). Both hydroxyl and carbonyl functionalities were detected by IR absorption at 3 444 and 1 651 cm−1, respectively. Upon careful comparison, NMR data of 2 ([Table 1]) were almost identical to those of 8 except for the replacement of an olefinic methyl at C-14 in 8 by a vinyl carbinol unit in 2 [13]. Detailed assignment of 1H-1H COSY and HMBC correlations (Fig. 1S, Supporting Information) revealed an α-chamigrane framework for 2. (Fig. 8S–13S)

The relative stereochemistry of 2 was determined by NOESY experiments. The NOESY correlations between H-2/H2–4 α, H-2/H3–15, and H2–4 α/H3–15 demonstrated that these protons were located on the same orientation, while both 2-Cl and 3-OH were located on the opposite orientation of the ring B. The relative configuration at C-6 was identical to that of (-)-8 based the NOE correlation between H2–1/H3–12, chemical shifts, and the optical rotation [α]D 25–46.0 (c 0.22) [13]. The methylene H2–14 (δ H 4.46 and 4.42) of 2 experienced a downfield shift of 0.2 ppm and was presented as an individual signal instead of superimposed as compared to that of 1 (δ H 4.24, H2–14). This could be due to the additional hydroxyl moiety in 2 at C-3, which results in a restricted rotation of the sigma bond between C-7 and C-14. Finally, judging from the co-occurrence of 2 and 8 in the same alga, the relative stereochemistry of the B ring in 2 is the same as that of 8. Therefore, 2S*, 3R*, and 6S* were assigned similarly to those of (-)-8. The natural product designated as laurencenone B [22] was incorrectly assigned due to discrepancies that existed between published 1H NMR data of the natural product and that of a synthetic compound [19]. Since then, no report of complete NMR and specific rotation measurements for the natural product laurencenone B (7) was found, therefore, herein, we reported its specific rotation and 1H and 13C NMR data. The specific rotation and 1H and 13C NMR data of 7 were consistent to semisynthetic and synthetic materials [13] [19].(Fig. 14S–15S)

The α-chamigrane-type sesquiterpenoids 1 and 2 showed strong cytotoxic activities against HeLa and P-388 cell lines with an IC50 ≤ 5.0 μg/mL ([Table 2]), whereas β-chamigrane-type sesquiterpenoids 36 displayed a much stronger cytotoxicity against cell lines HeLa, MCF-7, and P-388 with an IC50 ≤ 1.0 μg/mL. On the other hand, compounds 79 were found inactive against all cell lines. Compounds 1 and 2 exhibited weak activity against Bacillus cereus with MIC and MBC values of 250 and 1 000–1 250 μg/mL, respectively [Table 3]). In a previous literature, compound 3 was reported as having no activity against NO and TNF-α production in LPS-induced RAW 264.7 macrophages, and no antibacterial property on Mycobacterium bovis [12]. Compounds 4 and 6 were reported to show antileishmanial activity against Leishmania amazonensis on promastigotes (IC50 of 9.7 and 6.2 μg/mL, respectively) and amastigotes (IC50 of 4.5 and 3.9 μg/mL, respectively), but were not active against NO production by macrophages [15]. In addition, compounds 4 and 6 were also reported to exhibit cytotoxic activities against gastric carcinoma (IC50 of < 1.0 and 7.0 μg/mL, respectively), liver carcinoma (IC50 of < 1.0 μg/mL), and breast carcinoma (IC50 of < 1.0 and 1.5 μg/mL, respectively), while 5 showed an IC50 of 1.0, 0.25, and 1.0 μg/mL on non-small lung cancer, human colon carcinoma, and melanoma cells, respectively. Compounds 46, however, showed negligible antibacterial activity [24]

Table 2 Cytotoxicity of compounds 19 against cancer cell lines HeLa, MCF-7, and P-388.

Cells

IC50 (μg/mL)

1

2

3

4

5

6

7

8

9

HeLa

2.50

2.50

0.75

0.75

1.00

1.00

-

-

-

MCF-7

2.50

5.00

1.00

0.75

0.75

1.00

-

-

-

P-388

5.00

2.50

0.75

1.00

1.00

1.00

-

-

-

Table 3 Antibacterial activities of compounds 1 and 2 against clinical strains.

Strains

MIC (MBC) in μg/mL

1

2

Bacillus cereus

250 (1000)

250 (1250)

Escherichia coli

-

-

Salmonella typhi

> 500

> 500

Vibrio cholera

> 500

> 500

Positive control = kanamycin, with an MIC and MBC of 2.0 μg/mL


#

Materials and Methods

General experimental procedures

The 1H NMR (600 MHz) and 13C NMR (150 MHz) spectra were recorded on an NMR spectrometer (Jeol). The HRESIMS was acquired via LCMS-ESI-IT-TOF (Shimadzu). An AUTOPOL IV automatic polarimeter was used to measure the optical rotation (Rudolph Research Analytical). Infrared spectra were recorded on an FTIR (Thermo Nicolet). For preparative TLC (Kieselgel 60 F254, Merck), the spots were visualized by UV light (254 and 365 nm) and spraying with a 5% phosphomolybdic acid-ethanol solution. Column chromatography was performed with silica gel (Kieselgel 60, 70–230 mesh; Merck). All organic solvents for extraction and isolation were of analytical grade (Fisher Scientific). The HPLC solvent was HPLC grade (Fisher Scientific). The deuterated CDCl3 was purchased from Merck.


#

Plant material

Specimens of L. majuscula (Harvey) Lucas were collected from Mantanani Island, Sabah (06º59.728’N, 116º34.830’E) in November 2017. A voucher specimen (BORH39093) was deposited in the BORNEENSIS Collection of the Institute for Tropical Biology and Conservation, University of Malaysia, Sabah. Field identifications were done by Prof. Dr. Charles S. Vairappan, who is the corresponding author of this paper. Voucher specimens were examined by Assoc. Prof. Dr. Abe Tsuyoshi, Hokkaido University Museum, Sapporo, Japan.


#

Extraction and isolation

After air drying for 3 days, the alga (110 g) was extracted with methanol (MeOH). The resulting MeOH extract was concentrated in vacuo and partitioned between ethyl acetate (EtOAc) and H2O. The EtOAc fraction was washed with water, dried over anhydrous Na2SO4, and evaporated to leave a dark green oil (3.0 g). The EtOAc extract (1.5 g) was then fractionated by Si gel column chromatography with a step gradient (hexane and EtOAc). The fraction eluted with hexane-EtOAc (8:2) was subjected to preparative TLC with toluene to give compounds 4 (160 mg: 10.7%), 5 (99 mg: 6.6%), 6 (90 mg: 6.0%), 7 (101 mg: 6.7%), and 9 (41 mg: 2.7%). The fraction eluted with hexane-EtOAc (7:3) was subjected to preparative TLC with chloroform (CHCl3) to give 3 (41 mg: 2.7%). The fraction eluted with hexane-EtOAc (1:1) was subjected to preparative TLC with CHCl3 to give 8 (82 mg: 5.5%). The fraction eluted with EtOAc (100%) was subjected to preparative TLC with CHCl3-MeOH (95:5) to give 1 (16 mg: 1.1%) and 2 (15 mg: 1.0%). Compounds that were isolated using the preparative TLC technique were further purified using reverse phase HPLC with an ODS-3 column under acetonitrile, MeCN-H2O (50–100% MeCN), at 210 nm UV detection. Yields were calculated as a percentage of the EtOAc crude extract.

Lauremantanone A (1): colorless oil; [α]28 D  +22.3 (c 1.0, CHCl3); IR (neat) ν max 3420, 2930, 1650, 1455, 1318, 1078, and 979 cm−1; 1H and 13C NMR (CDCl3) spectral data: see [Table 1]; HRESIMS m/z 269.1305 [M + H]+ (calcd. for C15H22ClO2, 269.1303).

Lauremantanone B (2): colorless oil; [α]28 D -35.0 (c 0.5, CHCl3); IR (neat) ν max 3444, 2925, 1651, 1455, and 1118 cm−1; 1H and 13C NMR (CDCl3); spectral data: see [Table 1]; HRESIMS m/z 287.1412 [M + H]+ (calcd. for C15H24ClO3, 287.1409).

(+)-Laurencenone B (7): white powder; [α]25 D +39.4 (c 0.2, CHCl3); 1H NMR (CDCl3, 600 MHz) δ: 5.89 (1H, s), 2.54–2.62 (2H, br m), 2.27 (1H, d, J = 17.2 Hz), 2.16–2.20 (1H, br m), 2.02–2.09 (2H, br m), 1.97 (3H, s), 1.93 (1H, td, J = 12.7, 5.6 Hz), 1.81 (3H, s), 1.75–1.77 (1H, br m), 1.06 (3H, s), 0.97 (3H, s); 13C NMR (CDCl3, 150 MHz) δ: 198.1, 168.5, 129.7, 127.5, 126.3, 48.9, 46.4, 40.5, 36.3, 30.4, 30.2, 24.8, 23.8 (overlapped two signals), 19.7.


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Cytotoxic assay

The in vitro cytotoxicity assay was conducted against the cell lines human cervical epithelioid carcinoma (HeLa), human breast carcinoma (MCF-7), and murine lymphocytic leukemia (P-388). The tested concentrations were 100, 10, 1, 0.1, 0.01, and 0.001 µg/mL. The assay was carried out using a previous procedure [25]. Positive control experiments were conducted using H2O2 as the test chemical.


#

Antibacterial assay

The antibacterial assay was carried out using 96-well plates with a known microdilution method against the strains Bacillus cereus (QEB2018–01), Escherichia coli (QEB2018–02), Salmonella typhi (QEB2018–03), and Vibrio cholera (QEB2018–04) obtained from Queen Elizabeth General Hospital, Kota Kinabalu, Sabah, Malaysia. The tested concentrations were 500, 250, 125, 62.5, 31.3, 15.6, 7.8, 3.9, and 2.0 µg/mL. The assay was carried out using a previous procedure [6]. The positive control kanamycin (contained ≥ 98% kanamycin A) was purchased from Merck.


#
#

Supporting Information

NMR spectra of the new compounds are available as Supporting Information.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgements

The authors would like to acknowledge Assoc. Prof. Dr. Toshiyuki Hamada (Kagoshima University) and Assoc. Prof. Dr. Takahiro Ishii (University of the Ryukyus) for the database search. This study was supported from grants GL0070, ERGS0040-STWN-1–2013, and ESPEC Foundation for Global Environment Research and Technology (Charitable Trust).

Supporting Information

  • References

  • 1 Suzuki M, Vairappan CS. Halogenated secondary metabolites from Japanese species of the red algal genus Laurencia (Rhodomelaceae, Ceramiales). Curr Top Phytochemistry 2005; 5: 1-38
  • 2 Wang BG, Gloer JB, Ji NY, Zhao JC. Halogenated organic molecules of Rhodomelaceae origin: Chemistry and biology. Chem Rev 2013; 113: 3632-3685
  • 3 Ji NY, Wang BG. Nonhalogenated organic molecules from Laurencia algae . Phytochem Rev 2014; 13: 653-670
  • 4 Wanke T, Philippus AC, Zatelli GA, Vieira LFO, Lhullier C, Falkenberg M. C15 acetogenins from the Laurencia complex: 50 years of research–an overview. Revista Brasileira de Farmacognosia 2015; 25: 569-587
  • 5 Fenical W. Chemical variation in a new bromochamigrene derivative from the red seaweed Laurencia pacifica . Phytochemistry 1976; 15: 511-512
  • 6 Vairappan CS. Potent antibacterial activity of halogenated metabolites from Malaysian red algae, Laurencia majuscula (Rhodomelaceae, Ceramiales). Biomol Eng 2003; 20: 255-259
  • 7 Kamada T, Vairappan CS. Non-halogenated new sesquiterpenes from Bornean Laurencia snackeyi. Nat Prod Res 2017; 31: 333-340
  • 8 Kamada T, Phan CS, Vairappan CS. New anti-bacterial halogenated tricyclic sesquiterpenes from Bornean Laurencia majuscula (Harvey) Lucas. Nat Prod Res 2019; 33: 464-471
  • 9 Kamada T, Phan CS, Sien ST, Vairappan CS. Halogenated chamigrane sesquiterpenes from Bornean Laurencia majuscula . J Appl Phycol 2018; 30: 3373-3378
  • 10 Kamada T, Vairappan CS. New laurene-type sesquiterpene from Bornean Laurencia nangii. Nat Prod Commun 2015; 10: 843-844
  • 11 Ishii T, Nagamine T, Nguyen BCQ, Tawata S. Insecticidal and repellent activities of laurinterol from the Okinawan red alga Laurencia nidifica . Rec Nat Prod 2017; 11: 63-68
  • 12 da Silva Machado FL, Ventura TL, Gestinari LM, Cassano V, Resende JA, Kaiser CR, Lasunskaia EB, Muzitano MF, Soares AR. Sesquiterpenes from the Brazilian red alga Laurencia dendroidea J. Agardh. Molecules 2014; 19: 3181-3192
  • 13 Brennan MR, Erickson KL, Minott DA, Pascoe KO. Chamigrane metabolites from a Jamaican variety of Laurencia obtusa . Phytochemistry 1987; 26: 1053-1057
  • 14 Francisco MEY, Turnbull MM, Erickson KL. Cartilagineol, the fourth lineage of Laurencia-derived polyhalogenated chamigrene. Tetrahedron Lett 1998; 39: 5289-5292
  • 15 da Silva Machado FL, Lima WP, Bergmann BR, Gestinari LMS, Fujii MT, Paula JC, Costa SS, Lopes NP, Kaiser CR, Soares AR. Antileishmanial sesquiterpenes from the Brazilian red alga Laurencia dendroidea . Planta Med 2011; 77: 733-735
  • 16 Machado FLS, Duarte HM, Gestinari LMS, Cassano V, Kaiser CR, Soares AR. Geographic distribution of natural products produced by the red alga Laurencia dendroidea J. Agardh.. Chem Biodivers. 2016; 13: 845-851
  • 17 González AG, Martín JD, Martín VS, Norte M. Carbon-13 NMR application to Laurencia polyhalogenated sesquiterpenes. Tetrahedron Lett 1979; 29: 2719-2722
  • 18 White DE, Stewart IC, Grubbs RH, Stoltz BM. The catalytic asymmetric total synthesis of elatol. J Am Chem Soc 2008; 130: 810-811
  • 19 White DE, Stewart IC, Seashore-Ludlow BA, Grubbs RH, Stoltz BM. A general enantioselective route to the chamigrene natural product family. Tetrahedron 2010; 66: 4668-4686
  • 20 Faulkner DJ. Marine natural products. Nat Prod Rep 1988; 5: 613-663
  • 21 Vazquez JT, Chang M, Nakanishi K. Novel sesquiterpenes from Laurencia obtusa. Structure elucidation and absolute configuration and conformation based on circular dichroism. J Nat Prod 1988; 51: 1257-1260
  • 22 Kennedy DJ, Selby IA, Thomson RH. Chamigrane metabolites from Laurencia obtusa and L. scoparia . Phytochemistry 1988; 27: 1761-1766
  • 23 Liu CM, Zhu RL, Liu RH, Li HL, Shan L, Xu XK, Zhang WD. Cis-clerodane diterpenoids from the liverwort Gottschelia schizopleura and their cytotoxic activity. Planta Med 2009; 75: 1597-1601
  • 24 Wessels M, König GM, Wright AD. New natural product isolation and comparison of the secondary metabolite content of three distinct samples of the sea hare Aplysia dactylomela from Tenerife. J Nat Prod 2000; 63: 920-928
  • 25 WAJP Wijesinghe, Jeon YJ, Ramasamy P, Wahid MEA, Vairappan CS. Anticancer activity and mediation of apoptosis in human HL-60 leukemia cells by edible sea cucumber (Holothuria edulis) extract. Food Chem 2013; 139: 326-331

Correspondence

Prof. Dr. Charles Santhanaraju Vairappan
Laboratory of Natural Products Chemistry
Institute for Tropical Biology and Conservation
Universiti Malaysia Sabah
Jalan UMS
88400 Kota Kinabalu
Sabah
Malaysia
Phone: +60/88/320 000 ext. 2384   
Fax: +60 88 320 291   

  • References

  • 1 Suzuki M, Vairappan CS. Halogenated secondary metabolites from Japanese species of the red algal genus Laurencia (Rhodomelaceae, Ceramiales). Curr Top Phytochemistry 2005; 5: 1-38
  • 2 Wang BG, Gloer JB, Ji NY, Zhao JC. Halogenated organic molecules of Rhodomelaceae origin: Chemistry and biology. Chem Rev 2013; 113: 3632-3685
  • 3 Ji NY, Wang BG. Nonhalogenated organic molecules from Laurencia algae . Phytochem Rev 2014; 13: 653-670
  • 4 Wanke T, Philippus AC, Zatelli GA, Vieira LFO, Lhullier C, Falkenberg M. C15 acetogenins from the Laurencia complex: 50 years of research–an overview. Revista Brasileira de Farmacognosia 2015; 25: 569-587
  • 5 Fenical W. Chemical variation in a new bromochamigrene derivative from the red seaweed Laurencia pacifica . Phytochemistry 1976; 15: 511-512
  • 6 Vairappan CS. Potent antibacterial activity of halogenated metabolites from Malaysian red algae, Laurencia majuscula (Rhodomelaceae, Ceramiales). Biomol Eng 2003; 20: 255-259
  • 7 Kamada T, Vairappan CS. Non-halogenated new sesquiterpenes from Bornean Laurencia snackeyi. Nat Prod Res 2017; 31: 333-340
  • 8 Kamada T, Phan CS, Vairappan CS. New anti-bacterial halogenated tricyclic sesquiterpenes from Bornean Laurencia majuscula (Harvey) Lucas. Nat Prod Res 2019; 33: 464-471
  • 9 Kamada T, Phan CS, Sien ST, Vairappan CS. Halogenated chamigrane sesquiterpenes from Bornean Laurencia majuscula . J Appl Phycol 2018; 30: 3373-3378
  • 10 Kamada T, Vairappan CS. New laurene-type sesquiterpene from Bornean Laurencia nangii. Nat Prod Commun 2015; 10: 843-844
  • 11 Ishii T, Nagamine T, Nguyen BCQ, Tawata S. Insecticidal and repellent activities of laurinterol from the Okinawan red alga Laurencia nidifica . Rec Nat Prod 2017; 11: 63-68
  • 12 da Silva Machado FL, Ventura TL, Gestinari LM, Cassano V, Resende JA, Kaiser CR, Lasunskaia EB, Muzitano MF, Soares AR. Sesquiterpenes from the Brazilian red alga Laurencia dendroidea J. Agardh. Molecules 2014; 19: 3181-3192
  • 13 Brennan MR, Erickson KL, Minott DA, Pascoe KO. Chamigrane metabolites from a Jamaican variety of Laurencia obtusa . Phytochemistry 1987; 26: 1053-1057
  • 14 Francisco MEY, Turnbull MM, Erickson KL. Cartilagineol, the fourth lineage of Laurencia-derived polyhalogenated chamigrene. Tetrahedron Lett 1998; 39: 5289-5292
  • 15 da Silva Machado FL, Lima WP, Bergmann BR, Gestinari LMS, Fujii MT, Paula JC, Costa SS, Lopes NP, Kaiser CR, Soares AR. Antileishmanial sesquiterpenes from the Brazilian red alga Laurencia dendroidea . Planta Med 2011; 77: 733-735
  • 16 Machado FLS, Duarte HM, Gestinari LMS, Cassano V, Kaiser CR, Soares AR. Geographic distribution of natural products produced by the red alga Laurencia dendroidea J. Agardh.. Chem Biodivers. 2016; 13: 845-851
  • 17 González AG, Martín JD, Martín VS, Norte M. Carbon-13 NMR application to Laurencia polyhalogenated sesquiterpenes. Tetrahedron Lett 1979; 29: 2719-2722
  • 18 White DE, Stewart IC, Grubbs RH, Stoltz BM. The catalytic asymmetric total synthesis of elatol. J Am Chem Soc 2008; 130: 810-811
  • 19 White DE, Stewart IC, Seashore-Ludlow BA, Grubbs RH, Stoltz BM. A general enantioselective route to the chamigrene natural product family. Tetrahedron 2010; 66: 4668-4686
  • 20 Faulkner DJ. Marine natural products. Nat Prod Rep 1988; 5: 613-663
  • 21 Vazquez JT, Chang M, Nakanishi K. Novel sesquiterpenes from Laurencia obtusa. Structure elucidation and absolute configuration and conformation based on circular dichroism. J Nat Prod 1988; 51: 1257-1260
  • 22 Kennedy DJ, Selby IA, Thomson RH. Chamigrane metabolites from Laurencia obtusa and L. scoparia . Phytochemistry 1988; 27: 1761-1766
  • 23 Liu CM, Zhu RL, Liu RH, Li HL, Shan L, Xu XK, Zhang WD. Cis-clerodane diterpenoids from the liverwort Gottschelia schizopleura and their cytotoxic activity. Planta Med 2009; 75: 1597-1601
  • 24 Wessels M, König GM, Wright AD. New natural product isolation and comparison of the secondary metabolite content of three distinct samples of the sea hare Aplysia dactylomela from Tenerife. J Nat Prod 2000; 63: 920-928
  • 25 WAJP Wijesinghe, Jeon YJ, Ramasamy P, Wahid MEA, Vairappan CS. Anticancer activity and mediation of apoptosis in human HL-60 leukemia cells by edible sea cucumber (Holothuria edulis) extract. Food Chem 2013; 139: 326-331

Zoom Image
Fig. 1 Structures of sesquiterpenoids 1–9 from L. majuscula.