Mar. Drugs 2012, 10(11), 2415-2434; doi:10.3390/md10112415

Review
Natural Product Chemistry of Gorgonian Corals of the Family Plexauridae Distributed in the Indo-Pacific Ocean
Li-Hsueh Wang 1,2, Jyh-Horng Sheu 3,4, Shih-Yao Kao 1,2, Jui-Hsin Su 1,2,3, Yung-Husan Chen 1, Yu-Hsin Chen 1,2, Yin-Di Su 1,3, Yu-Chia Chang 1,4, Lee-Shing Fang 5, Wei-Hsien Wang 1,3, Yang-Chang Wu 6,7,8,* and Ping-Jyun Sung 1,2,3,*
1
National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan; Email: wanglh@nmmba.gov.tw (L.-H.W.); sweetcloud0906@gmail.com (S.-Y.K.); x2219@nmmba.gov.tw (J.-H.S.); tony_chen72001@yahoo.com.tw (Y.-H.C.); kb5634@yahoo.com.tw (Y.-H.C.); gobetter04@yahoo.com.tw (Y.-D.S.); jay0404@gmail.com (Y.-C.C.); jay0404@gmail.com (W.-H.W.)
2
Graduate Institute of Marine Biotechnology and Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan
3
Department of Marine Biotechnology and Resources and Division of Marine Biotechnology, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan; Email: sheu@mail.nsysu.edu.tw
4
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan
5
Department of Sport, Health and Leisure, Cheng Shiu University, Kaohsiung 833, Taiwan; Email: lsfang@csu.edu.tw
6
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan
7
Natural Medicinal Products Research Center, China Medical University Hospital, Taichung 404, Taiwan
8
Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan
*
Authors to whom correspondence should be addressed; Email: yachwu@mail.cmu.edu.tw (Y.-C.W.); pjsung@nmmba.gov.tw (P.-J.S.); Tel.: +886-4-220-57153 (Y.-C.W.); +886-8-882-5037 (P.-J.S.); Fax: +886-4-220-60248 (Y.-C.W.); +886-8-882-5087 (P.-J.S.).
Received: 13 September 2012; in revised form: 10 October 2012 / Accepted: 16 October 2012 /
Published: 1 November 2012

Abstract

: The structures, names, bioactivities and references of 105 natural products obtained from gorgonian corals belonging to the family Plexauridae with an Indo-Pacific distribution are described in this review. All compounds mentioned in this review were obtained from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella.
Keywords:
Plexauridae; gorgonian; Astrogorgia; Bebryce; Echinomuricea; Euplexaura; Menella

1. Introduction

Over the past thirty-four years, 105 natural products have been reported from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella with an Indo-Pacific distribution, all belonging to the family Plexauridae (Cnidaria: Anthozoa: Gorgonacea) [1]. This review summarizes the structures, names, bioactivities and references of all compounds in tabular form.

2. Natural Products from Gorgonian Corals Belonging to the Family Plexauridae

2.1. Genus Astrogorgia

Astrogorgia sp.

A novel 9,10-secosterol, astrogorgiadiol (1), and a new eunicellin-based diterpenoid, astrogorgin (2), along with a known eunicellin, ophirin (3), were isolated from the gorgonian Astrogorgia sp., collected at Okino-shima Island off Shikoku, Japan [2] (Table 1). The structures of new metabolites 1 and 2 were established by spectroscopic methods and by comparison of the spectral data with those of related analogs. Compounds 13 were found to display activity to inhibit cell division of the fertilized eggs of the starfish Asterina pectinifera.

Table 1. The natural products from Astrogorgia sp.

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Table 1. The natural products from Astrogorgia sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i0011AstrogorgiadiolInhibited cell division of fertilized starfish (Asterina pectinifera) eggs at a concentration of 50 μg/mL. IC50 (ALK, Aurora-B, AXL, FAK, IGF1-R, MEK1 wt, MET wt, SRC, VEGF-R2) = 7.6, 25.1, 16.9, 13.2, 2.8, 48.9, 78.0, 1.9, 4.4 μM.[2,3]
Marinedrugs 10 02415 i0022Astrogorgin Eunicellins 2 and 3 inhibited cell division of fertilized starfish (Asterina pectinifera) eggs at a concentration of 10 μg/mL.[2]
Marinedrugs 10 02415 i0033Ophirin [2]

Furthermore, twenty-one 9,10-secosterols, including thirteen new metabolites, astrogorgols A–M (416), along with eight known compounds, calicoferols A–C (1719), E (20), G (21), I (22), 24-exomethylenecalicoferol E (23), and astrogorgiadiol (1) and a new steroid, astrogorgol N (24), were isolated from the gorgonian Astrogorgia sp. collected from the inner coral reef in Beibuwan Bay, Guangxi province, China [3] (Table 2). The structures of new sterols 416 and 24 were determined by spectroscopic methods and by comparison of their spectral and physical data with those reported in the literature. Secosterols 1, 9, 17, 18 and 23 showed inhibitory effects against a series of protein kinases. The structures of calicoferols B (18) [3,4], C (19), E (20) [3,5] and I (22) [3,6] that are shown in reference 3 should be revised as presented in the original literature.

Table 2. The natural products from Astrogorgia sp.

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Table 2. The natural products from Astrogorgia sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i0044Astrogorgol A (R1 = H, R2 = SC1) [3]
5Astrogorgol B (R1 = H, R2 = SC2) [3]
6Astrogorgol C (R1 = OH, R2 = SC1) [3]
7Astrogorgol D (R1 = OH, R2 = SC3) [3]
17Calicoferol A (R1 = H, R2 = SC3)IC50 (ALK, AXL, FAK, [3]
IGF1-R, MET wt, SRC,
VEGF-R2) = 4.2, 14.7, 9.9, 2.4,
47.6, 2.2, 4.6 μM.
20Calicoferol E (R1 = H, R2 = SC5) [3,5]
22Calicoferol I (R1 = OH, R2 = SC5) [3,6]
2324-Exomethylenecalicoferol EIC50 (ALK, AXL, FAK, [3]
(R1 = H, R2 = SC4) IGF1-R, MET wt, SRC,
VEGF-R2) = 4.4, 20.2, 10.7,
2.3, 27.5, 1.5, 4.9 μM.
Marinedrugs 10 02415 i0058Astrogorgol E (R1 = H, R2 = SC1, R3 = β-OH) [3]
9Astrogorgol F (R1 = H, R2 = SC3, R3 = β-OH)IC50 (ALK, [3]
Aurora-B, AXL,
FAK, IGF1-R, MET
wt, SRC, VEGF-R2)
= 9.3, 38.1, 21.9,
16.9, 3.2, 34.0, 2.4,
5.0 μM
10Astrogorgol G (R1 = H, R2 = SC5, R3 = β-OH) [3]
11Astrogorgol H (R1 = H, R2 = SC3, R3 = α-OH) [3]
12Astrogorgol I (R1 = H, R2 = SC2, R3 = α-OH) [3]
13Astrogorgol J (R1 = H, R2 = SC6, R3 = α-OH) [3]
14Astrogorgol K (R1 = H, R2 = SC7, R3 = α-OH) [3]
15Astrogorgol L (R1 = OH, R2 = SC3, R3 = α-OH) [3]
16Astrogorgol M (R1 = OH, R2 = SC4, R3 = α-OH) [3]
18Calicoferol B (R1 = OH, R2 = SC5, R3 = α-OH) IC50 (ALK, AXL, [3,4]
FAK, IGF1-R, MET
wt, SRC, VEGF-R2)
= 4.7, 32.6, 9.6, 2.5,
71.5, 2.2, 6.0 μM.
19Calicoferol C (R1 = H, R2 = SC4, R3 = α-OH) [3,5]
21Calicoferol G (R1 = H, R2 = SC8, R3 = α-OH) [3]
Marinedrugs 10 02415 i00624Astrogorgol N (R = SC7) [3]
Marinedrugs 10 02415 i007

2.2. Genus Bebryce

2.2.1. Bebryce grandicalyx

In 1998, a new unstable sesquiterpene, bebryazulene (25), with a guaiane skeleton, was isolated from the gorgonian coral B. grandicalyx, collected at the Prevoyante Reef, Lagoon of Mayotte, Comoros Islands, Indian Ocean [7] (Table 3). The structure of guaiane 25 was assigned by spectroscopic methods. This metabolite was labile and reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to yield a triazolinedione adduct.

Table 3. The natural product from B. grandicalyx.

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Table 3. The natural product from B. grandicalyx.
StructureNo.NameRef.
Marinedrugs 10 02415 i00825Bebryazulene[7]

2.2.2. Bebryce indica

B. indica, a gorgonian species collected off the coast of Sanya, Hainan province, China, was found to contain a new steroidal glycoside, bebrycoside (26) [8] (Table 4). The main structure of 26 was determined by spectral data analysis, although the stereochemistry of the C-25 chiral carbon was not determined. Bebrycoside (26) is the first steroidal glycoside to be isolated from the genus Bebryce.

Table 4. The natural product from B. indica.

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Table 4. The natural product from B. indica.
StructureNo.NameRef.
Marinedrugs 10 02415 i00926Bebrycoside[8]

2.2.3. Bebryce sp.

Bebryceoid A (27), a new trihydroxysteroid, was isolated from gorgonian Bebryce sp., collected off the coast of Pingtung, southern Taiwan [9] (Table 5). The structure of steroid 27 was assigned by spectroscopic methods. Bebryceoid A (27) exhibited weak cytotoxicity toward P388D1 and DLD-1 tumor cells.

Table 5. The natural product from Bebryce sp.

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Table 5. The natural product from Bebryce sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i01027Bebryceoid AED50 (P388D1, DLD-1, CCRF-CEM, HL-60) = 18.5, 7.2, >40, >40 μg/mL[9]

2.3. Genus Echinomuricea

Echinomuricea sp.

Two sesquiterpenoids, including new natural product (7S,10R)-(+)-10,11-epoxycurcuphenol (28) and known metabolite (+)-curcuphenol (29) [10], along with a new labdane-type diterpenoid, echinolabdane A (30), a new sterol, 6-epi-yonarasterol B (31) [11], a new clerodane-type diterpenoid, echinoclerodane A (32) [12] and a new halimane-type diterpenoid, echinohalimane A (33) [13], were isolated from the gorgonian coral Echinomuricea sp., collected off the coast of southern Taiwan (Table 6). The structures of metabolites 2833 were elucidated by spectroscopic methods. Echinolabdane A (30) possesses a novel tetracyclic skeleton with an oxepane ring joined to an α,β-unsaturated-γ-lactone ring by a hemiketal moiety [11]. Echinolabdane A (30), echinoclerodane A (32) and echinohalimane A (33) are the first labdane-, clerodane- and halimane-type diterpenoids to be obtained from marine organisms belonging to the phylum Cnidaria, respectively [11,12,13].

Table 6. The natural products from Echinomuricea sp.

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Table 6. The natural products from Echinomuricea sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i01128(7 S,10R)-(+)-10,11-EpoxycurcuphenolShowed inhibitory effects on the generation of superoxide anions (inhibition rate 35.3%) and the release of elastase (inhibition rate 38.8%) at a concentration of 10 μg/mL. [10]
Marinedrugs 10 02415 i01229(+)-CurcuphenolShowed inhibitory effects on the generation of superoxide anion (inhibition rate 36.9%) and the release of elastase (inhibition rate 83.6%) at a concentration of 10 μg/mL. ED50 (DLD-1, CCRF-CEM) = 12.5, 11.8 μg/mL.[10]
Marinedrugs 10 02415 i01330Echinolabdane ANot active in terms of inhibition of the generation of superoxide anions (inhibition rate 2.5%) or the release of elastase (inhibition rate 1.8%) at a concentration of 10 μg/mL. IC50 (HL-60) = 19.1 μg/mL.[11]
Marinedrugs 10 02415 i014316- epi-Yonarasterol BShowed significant inhibitory effects on the generation of superoxide anions (IC50 = 3.0 μg/mL) and the release of elastase (IC50 = 1.1 μg/mL).[11]
Marinedrugs 10 02415 i01532Echinoclerodane AShowed inhibitory effects on the generation of superoxide anions (inhibition rate 68.6%) and the release of elastase (inhibition rate 35.4%) at a concentration of 10 μg/mL. IC50 (K562, MOLT-4, HL-60, DLD-1, LoVo, DU-145) = 37.1, 13.2, 14.9, 23.4, 21.7, 53.9 μg/mL.[12]
Marinedrugs 10 02415 i01633Echinohalimane AShowed a significant inhibitory effect on the release of elastase (IC50 = 0.4 μg/mL).IC50 (K562, MOLT-4, HL-60, DLD-1, LoVo) = 6.3, 2.1, 2.1, 1.0, 0.6 μg/mL.[13]

In biological activity experiments, sesquiterpenoid 29 displayed a significant inhibitory effect on the release of elastase by human neutrophils. This compound also exhibited weak cytotoxicity toward DLD-1 and CCRF-CEM tumor cells [9]. Steroid 31 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils [11]. Clerodane 32 exhibited weak cytotoxicity toward MOLT-4 and HL-60 tumor cells and displayed a significant inhibitory effect on the generation of superoxide anions by human neutrophils [12]. Halimane 33 exhibited cytotoxicity toward K562, MOLT-4, HL-60, DLD-1 and LoVo tumor cells and displayed a significant inhibitory effect on the release of elastase by human neutrophils [13].

2.4. Genus Euplexaura

2.4.1. Euplexaura anastomosans

Four new steroids of the cholestane class, anastomosacetals A–D (3437), were obtained from the gorgonian coral E. anastomosans, collected off the shore of Keomun Island, South Sea Korea [14] (Table 7). The structures of steroids 3437 were determined by spectroscopic methods, and these four compounds are the first examples of marine steroids possessing an unusual hemiacetal linkage formed by oxidation of the C-21 methyl group.

In addition, seven new moritoside class farnesylhydroquinone glycosides, euplexides A–G (3844), were isolated from E. anastomosans [15,16] (Table 7). The structures of glycosides 3844, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods. Compounds 3844 exhibited moderate cytotoxicity and antioxidant activity as well as an inhibitory effect against PLA2.

Table 7. The natural products from E. anastomosans.

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Table 7. The natural products from E. anastomosans.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i01734Anastomosacetal ASteroids 3437 were not toxic to P-388 cells or brine-shrimp larva.[14]
35Anastomosacetal B (4,5-dihydro)[14]
36Anastomosacetal C (1,2-dihydro)[14]
37Anastomosacetal D (1,2,4,5-tetrahydro)[14]
Marinedrugs 10 02415 i01838Euplexide A (R1 = OH, R2 = R3 = OAc)Glycosides 3840, 43, 44 exhibited cytotoxicity toward K462 cells (IC50 = 2.6, 3.1, 5.2, 8.7, 11.3 μg/mL). Glycosides 3840 displayed antioxidant activity of 3.4, 3.6 and 3.5 times, respectively, that of superoxide dismutase (SOD) at a concentration of 10 μg/300 μL. Glycosides 38, 39, 43, 44 exhibited 52, 71, 47 and 58%, respectively, inhibition of PLA2 at a concentration of 50 μg/mL. [15]
39Euplexide B (R1 = R2 = R3 = OAc)[15]
40Euplexide C (R1 = H, R2 = R3 = OAc)[15]
43Euplexide F (R1 = H, R2 = OH, R3 = OAc)[16]
44Euplexide G (R1 = H, R2 = OAc, R3 = OH)[16]
Marinedrugs 10 02415 i01941Euplexide DIC50 (K462) = 8.1 μg/mL.[15]
Marinedrugs 10 02415 i02042Euplexide EIC50 (K462) = 9.4 μg/mL. Displayed antioxidant activity of 3.1 times that of superoxide dismutase (SOD) at a concentration of 10 μg/300 μL.[15]

2.4.2. Euplexaura erecta

A prostaglandin derivative, PGF (45), was isolated from the gorgonian coral E. erecta collected at Shimoda, Sagami Bay, Japan [17] (Table 8), and this compound was proven to be the active component in E. erecta. This finding is the first demonstration that gorgonian corals containing prostaglandins are not limited to species in the Caribbean area.

Furthermore, a bluish-violet oil, guaiazulene (46), was isolated from E. erecta collected at Enoshima Island, Kanagawa, Japan [18] (Table 8). The structure of guaiazulene (46) from E. erecta was determined by spectroscopic methods and by comparison of the spectral data with those of reported data. This is the first isolation of guaiazulene from an animal, and this compound showed mild antimicrobial activity [18].

Table 8. The natural products from E. erecta.

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Table 8. The natural products from E. erecta.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i02145PGF Contracting activity towards isolated guinea-pig ileum strips.[17]
Marinedrugs 10 02415 i02246GuaiazuleneShowed mild activity against fungi, gram-positive and gram-negative bacteria.[18]

2.4.3. Euplexaura flava

Four new unnamed fatty acid derivatives 4750, which contain a butenolide moiety, were isolated from the gorgonian coral E. flava, collected at the coral reef of Ishigaki Island, Okinawa, Japan. The structures of butenolides 4750 were elucidated by spectroscopic and chemical methods [19] (Table 9).

Table 9. The natural products from E. flava.

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Table 9. The natural products from E. flava.
StructureNo.NameRef.
Marinedrugs 10 02415 i02347R = SC1[19]
48R = SC2[19]
49R = SC3[19]
50R = SC4[19]

2.4.4. Euplexaura nuttingi

Six new tetraprenylated purine alkaloids, nuttingins A–F (5156), were isolated together with five new compounds, malonganenones D–H (5761), and three known metabolites, malonganenones A–C (6264), from the gorgonian coral E. nuttingi collected in Uvinage, Pemba Island, Tanzania. The structures of compounds 5164 were elucidated by interpretation of spectral data [20] (Table 10). Mixtures of nuttingins A and B (51 and 52), C–E (5355), malonganenones D and E (57 and 58), and F and G (59 and 60) have been found to inhibit growth of K562 and UT7 tumor cells. Nuttingins A–E (5155) and malonganenones D–H (5761) induce apoptosis in transformed mammalian cells [20].

Table 10. The natural products from E. nuttingi.

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Table 10. The natural products from E. nuttingi.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i02451Nuttingin A (R = SC1)Compounds 5155 and 5761 induce apoptosis in transformed mammalian cells at a concentration of 1.25 μg/mL. Mixtures of compounds 51 and 52 displayed inhibitory activity on the proliferation of UT7 and K562 cell lines, although they were approximately 3-fold less potent than mixtures of compounds 5355.[20]
52Nuttingin B (R = SC3)[20]
Marinedrugs 10 02415 i02553Nuttingin C (R = SC1)Mixtures of compounds 5355 induced 50% inhibition of cell growth in UT7 cells and 30% in K562 cells after 48 h of exposure at a concentration of 0.4 μg/mL.[20]
54Nuttingin D (R = SC2)[20]
55Nuttingin E (R = SC3)[20]
Marinedrugs 10 02415 i02656 Nuttingin F (R = SC2) [20]
Marinedrugs 10 02415 i02757Malonganenone D (R = SC1)Mixtures of compounds 57 and 58 displayed inhibitory activity on the proliferation of UT7 and K562 cell lines, although they were approximately 3-fold less potent than mixtures of compounds 5355.[20]
58Malonganenone E (R = SC2)[20]
62Malonganenone A (R = SC3)[20]
Marinedrugs 10 02415 i02859Malonganenone F (R = SC1)Mixtures of compounds 59 and 60 displayed inhibitory activity on the proliferation of UT7 and K562 cell lines, although they were approximately 3-fold less potent than mixtures of compounds 5355.[20]
60Malonganenone G (R = SC2)[20]
63Malonganenone B (R = SC3)[20]
Marinedrugs 10 02415 i02961 Malonganenone H (R = SC2) [20]
64Malonganenone C (R = SC3) [20]
Marinedrugs 10 02415 i030

2.4.5. Euplexaura sp.

Moritoside (65), a new hydroquinone glycoside derivative was isolated from the gorgonian Euplexaura sp., collected near Morito beach in the Gulf of Sagami, Japan. The structure of glycoside 65 was determined by spectroscopic and chemical methods [21] (Table 11). This is the first example of the occurrence of D-altrose in natural products, and this compound inhibits the first cell division of fertilized starfish (Asterina pectinifera) eggs.

Table 11. The natural product from Euplexaura sp.

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Table 11. The natural product from Euplexaura sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i03165MoritosideInhibits the first cell division of fertilized starfish (Asterina pectinifera) eggs at a concentration of 1 μg/mL.[21]

2.5. Genus Menella

2.5.1. Menella spinifera

The gorgonian M. spinifera collected off the South China Sea was found to contain six known compounds, including batyl alcohol (66) [22,23], picolinic acid N-methyl betaine (67) [23,24], n-hexadecanol (68) [23], 3β-hydroxy-5α-pregnane-20-one (69) [23], 9H-purin-6-amino-N-9-dimethyl (70) [23] and thymidine (71) [23] (Table 12). The structures of compounds 6671 were elucidated by spectroscopic methods.

Table 12. The natural products from M. spinifera.

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Table 12. The natural products from M. spinifera.
StructureNo.NameRef.
Marinedrugs 10 02415 i03266Batyl alcohol[22,23]
Marinedrugs 10 02415 i03367Picolinic acid N-methyl betaine[23,24]
Marinedrugs 10 02415 i03468n-Hexadecanol [23]
Marinedrugs 10 02415 i03569 3β-Hydroxy-5α-pregnane-20-one [23]
Marinedrugs 10 02415 i036709 H-Purin-6-amino-N-9-dimethyl [23]
Marinedrugs 10 02415 i03771Thymidine [23]

2.5.2. Menella verrucosa

Four new highly-oxygenated guaiane lactones, menverins A–D (7275) [25], and two new polyoxygenated steroids, menellsteroids A (76) and B (77) [26] (Table 13), were isolated from the gorgonian M. verrucosa, collected along the coast of Xiaodong Hai, Hainan province, China. The structures of metabolites 7277 were established by spectroscopic methods. In a later study, menellsteroid A (76) was found to exhibit modest anti-inflammatory inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages [27].

Table 13. The natural products from M. verrucosa.

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Table 13. The natural products from M. verrucosa.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i03872Menverin A (R1 = α-H, R2 = β-OH, R3 = α-methyl) [25]
73Menverin B (R1 = α-H, R2 = β-methyl, R3 = α-OH) [25]
74Menverin C (R1 = α-OH, R2 = β-OH, R3 = α-methyl) [25]
75Menverin D (R1 = R2 = β-OH, R3 = α-methyl)[25]
Marinedrugs 10 02415 i03976Menellsteroid A (22,23-dihydro)Exhibited a modest inhibitory effect with an IC50 of 33.9 μM compared to the positive control aminoguanidine, with an IC50 = 25.0 μM.[26,27]
77 Menellsteroid B [26]

2.5.3. Menella sp.

Li et al., isolated four new highly-oxygenated guaiane lactones, 1-epimenverin B (78), menverin F (79), 1-deoxymenverin F (80) and menverin G (81), along with two known guaiane analogs, menverins B (73) and C (74), from the gorgonian Menella sp., collected off the Lingshui Bay, Hainan province, China [28] (Table 14). The structures of new guaianes 7881 were elucidated by spectroscopic methods and by comparison with those of known analogs.

Table 14. The natural products from Menella sp.

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Table 14. The natural products from Menella sp.
StructureNo.NameRef.
Marinedrugs 10 02415 i04078 1-Epimenverin B [28]
Marinedrugs 10 02415 i04179Menverin F (R = α-OH)[28]
801-Deoxymenverin F (R = α-H)[28]
Marinedrugs 10 02415 i04281Menverin G[28]

A chemical investigation of the gorgonian Menella sp., collected off Meishan Island, Hainan province, China, resulted in a novel highly-oxygenated racemate with a C8 skeleton, menellin A (82), a new tetrahydroxysteroid, menellsteroid C (83), a new natural product, 1β,3β,5α-trihydroxy-cholestan-6-one (84) and seven known compounds, menellsteroid A (76), cholestan-3β,5α,6β-triol (85), cholestan-1β,3β,5α,6β-tetrol (86), nephalsterol (87), cholestan-3β-5-en-6-one (88) and junceellolides B (89) and D (90) [27] (Table 15). The structures of the above compounds were elucidated by spectroscopic methods and by comparison of the spectral data with those of known analogs. The structure, including the relative stereochemistry, of menellin A (82) was further confirmed by single-crystal X-ray diffraction analysis. As already reported for menellsteroid A (76), menellin A (82) exhibited modest anti-inflammatory inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages.

Seven pregnane steroids, 3α-hydroxy-5β-pregnan-20-one (91), 3β-hydroxy-5α-pregnan-20-one (92), 3β-hydroxy-pregnan-5-en-20-one (93), 5β-pregnan-3,20-dione (94), 5α-pregnan-3,20-dione (95), pregnan-4-en-3,20-dione (96) and pregnan-1,4-dien-3,20-one (97), were isolated from the gorgonian Menella sp., collected off Meishan Island, Sanya Bay, Hainan province, China [29] (Table 16). The structures of steroids 9197 were elucidated by spectroscopic methods and by comparison with those of known analogs. The NMR data of steroid 97 are reported for the first time in this study.

Table 15. The natural products from Menella sp.

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Table 15. The natural products from Menella sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i04382Menellin AExhibited a modest inhibitory effect (IC50 = 71.3 μM) compared to the positive control aminoguanidine (IC50 = 25.0 μM). There were no obvious scavenging effects for compounds 76 and 8290 on the antioxidant capacity in a radical DPPH free-radical assay. [27]
Marinedrugs 10 02415 i04483Menellsteroid C (R1 = H, R2 = OH)[27]
85Cholestan-3β,5α,6β-triol (R1 = R2 = H)[27]
86Cholestan-1β,3β,5α,6β-tetrol (R1 = OH, R2 = H)[27]
Marinedrugs 10 02415 i04584Menellsteroid D (1β,3β,5α-trihydroxycholestan-6-one)[27]
Marinedrugs 10 02415 i04687 Nephalsterol[27]
Marinedrugs 10 02415 i04788Cholestan-3β-5-en-6-one [27]
Marinedrugs 10 02415 i04889Junceellolide B [27]
Marinedrugs 10 02415 i04990Junceellolide D[27]
Table 16. The natural products from Menella sp.

Click here to display table

Table 16. The natural products from Menella sp.
StructureNo.NameRef.
Marinedrugs 10 02415 i050913α-Hydroxy-5β-pregnan-20-one (R1 = α-OH, R2 = β-H)[29]
923β-Hydroxy-5α-pregnan-20-one (R1 = β-OH, R2 = α-H) [29]
Marinedrugs 10 02415 i051933β-Hydroxy-pregnan-5-en-20-one [29]
Marinedrugs 10 02415 i052945β-Pregnan-3,20-dione (R = β-H)[29]
955α-Pregnan-3,20-dione (R = α-H) [29]
Marinedrugs 10 02415 i05396Pregnan-4-en-3,20-dione (1,2-dihydro)[29]
97Pregnan-1,4-dien-3,20-dione [29]

Eight sesquiterpenoids, including seven new compounds, (–)-hydroxylindestrenolide (98) [30], menelloides A–E (99103) [31,32,33] and (+)-chloranthalactone B (104) [31], along with a known metabolite, seco-germacrane anhydride (105) [34] (Table 17), were isolated from the Formosan gorgonian Menella sp., collected by trawling off the coast of southern Taiwan. (–)-Hydroxy-lindestrenolide (98) and (+)-chloranthalactone B (104) were proven to be enantiomers of the known sesquiterpenoids (+)-hydroxylindestrenolide and chloranthalactone B, respectively [30,31]. Menelloide A (99) was found to possess a new carbon skeleton [31]. Seco-germacrane anhydride (105) was a known metabolite and there have been no reports of seco-germacrane anhydride (105) being obtained from any marine organism previously [34]. Several of these compounds displayed inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.

Table 17. The natural products from Menella sp.

Click here to display table

Table 17. The natural products from Menella sp.
StructureNo.NameBiological ActivityRef.
Marinedrugs 10 02415 i05498(–)-HydroxylindestrenolideDisplayed a weak inhibitory effect on the generation of superoxide anions (inhibition rate 13.4%) at a concentration of 10 μg/mL.[30]
Marinedrugs 10 02415 i05599Menelloide ADisplayed a weak inhibitory effect on the generation of superoxide anions (27.6%) at a concentration of 10 μg/mL. [31]
Marinedrugs 10 02415 i056100Menelloide BNot active in terms of inhibition of the generation of superoxide anions (inhibition rate 2.9%) and the release of elastase (inhibition rate 0.7%) at a concentration of 10 μg/mL. [31]
Marinedrugs 10 02415 i057101Menelloide C [32]
Marinedrugs 10 02415 i058102Menelloide DDisplayed a weak inhibitory effect on the release of elastase (inhibition rate 10.5%) at a concentration of 10 μg/mL. [32]
Marinedrugs 10 02415 i059103Menelloide EDisplayed weak inhibitory effects on the generation of superoxide anions (inhibition rate 19.9%) and the release of elastase (inhibition rate 27.0%) at a concentration of 10 μg/mL.[33]
Marinedrugs 10 02415 i060104 (+)-Chloranthalactone BDisplayed a weak inhibitory effect on the generation of superoxide anions (inhibition rate 16.5%), but was not active in terms of inhibition of the release of elastase (inhibition rate 6.6%) at a concentration of 10 μg/mL.[31]
Marinedrugs 10 02415 i061105 Seco-germacrane anhydride [34]

3. Conclusions

The search for bioactive natural products from marine organisms has been remarkably successful, and octocorals have been proven to be rich sources of natural products with potential biomedical application [35,36,37]. In particular, the data reported in this review indicate that terpenoid and steroid derivatives represent the major chemical classes occurring in Indo-Pacific octocoral species belonging to the family Plexauridae. Among the 105 isolated metabolites, in fact, 49 compounds are terpenoid analogs (46.7%) and 45 compounds are steroid metabolites (42.9%). These compounds continue to attract attention owing to their structural novelty, complexity and interesting bioactivities.

Acknowledgments

This work was supported by grants from the National Dong Hwa University; the National Museum of Marine Biology and Aquarium (Grant No. 10120022); the Division of Marine Biotechnology, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, (Grant No. 00C-0302-05); the Department of Health, Executive Yuan, Taiwan (Grant No. DOH101-TD-C-111-002); and the National Science Council (Grant No. NSC 101-2325-B-291-001, 100-2325-B-291-001, 101-2320-B-291-001-MY3 and 98-2320-B-291-001-MY3), Taiwan, awarded to Yang-Chang Wu and Ping-Jyun Sung.

References

  1. Fabricius, K.; Alderslade, P. Soft Corals and Sea Fans: A Comprehensive Guide to the Tropical Shallow-Water Genera of the Central-West Pacific, the Indian Ocean and the Red Sea, 1st ed.; Australian Institute of Marine Science: Queensland, Australia, 2001; pp. 59–60, 190–213.
  2. Fusetani, N.; Nagata, H.; Hirota, H.; Tsuyuki, T. Astrogorgiadiol and astrogorgin, inhibitors of cell division in fertilized starfish eggs, from a gorgonian Astrogorgia sp. Tetrahedron Lett. 1989, 30, 7079–7082, doi:10.1016/S0040-4039(01)93428-8.
  3. Lai, D.; Yu, S.; van Ofwegen, L.; Totzke, F.; Proksch, P.; Lin, W. 9,10-Secosteroids, protein kinase inhibitors from the Chinese gorgonian Astrogorgia sp. Bioorg. Med. Chem. 2011, 19, 6873–6880, doi:10.1016/j.bmc.2011.09.028.
  4. Ochi, M.; Yamada, K.; Kotsuki, H.; Shibata, K. Calicoferols A and B, two novel secosterols possessing brine-shrimp lethality from the gorgonian Calicogorgia sp. Chem. Lett. 1991, 20, 427–430.
  5. Seo, Y.; Shin, J.; Song, J.-I. New secosteroids from an undescribed gorgonian of the genus Muricella. J. Nat. Prod. 1995, 58, 1291–1296, doi:10.1021/np50122a024.
  6. Seo, Y.; Cho, K.W.; Chung, H.; Lee, H.-S.; Shin, J. New secosteroids from a gorgonian of the genus Muricella. J. Nat. Prod. 1998, 61, 1441–1443, doi:10.1021/np980220e.
  7. Aknin, M.; Rudi, A.; Kashman, Y.; Gaydou, E.M. Bebryazulene, a new guaiane metabolite from the Indian Ocean gorgonian coral, Bebryce grandicalyx. J. Nat. Prod. 1998, 61, 1286–1287, doi:10.1021/np980063j.
  8. Yang, J.; Qi, S.-H.; Zhang, S.; Xiao, Z.-H.; Li, Q.-X. Bebrycoside, a new steroidal glycoside from the Chinese gorgonian coral Bebryce indica. Pharmazie 2007, 62, 154–155.
  9. Sung, P.-J.; Liu, C.-Y. New 3β,5α,6β-trihydroxysteroids from the octocorals Bebryce sp. (Plexauridae) and Carijoa sp. (Clavulariidae). Chem. Pharm. Bull. 2010, 58, 1240–1242, doi:10.1248/cpb.58.1240.
  10. Chung, H.-M.; Hwang, T.-L.; Wang, W.-H.; Fang, L.-S.; Sung, P.-J. Curcuphenol derivatives from the gorgonian Echinomuricea sp. Heterocycles 2009, 78, 2595–2600, doi:10.3987/COM-09-11771.
  11. Chung, H.-M.; Hong, P.-H.; Su, J.-H.; Hwang, T.-L.; Lu, M.-C.; Fang, L.-S.; Wu, Y.-C.; Li, J.-J.; Chen, J.-J.; Wang, W.-H.; Sung, P.-J. Bioactive compounds from a gorgonian coral Echinomuricea sp. (Plexauridae). Mar. Drugs 2012, 10, 1169–1179, doi:10.3390/md10051169.
  12. Cheng, C.-H.; Chung, H.-M.; Hwang, T.-L.; Lu, M.-C.; Wen, Z.-H.; Kuo, Y.-H.; Wang, W.-H.; Sung, P.-J. Echinoclerodane A: A new bioactive clerodane-type diterpenoid from a gorgonian coral Echinomuricea sp. Molecules 2012, 17, 9443–9450, doi:10.3390/molecules17089443.
  13. Chung, H.-M.; Hu, L.-C.; Yen, W.-H.; Su, J.-H.; Lu, M.-C.; Hwang, T.-L.; Wang, W.-H.; Sung, P.-J. Echinohalimane A, a bioactive halimane-type diterpenoid from a formosan gorgonian Echinomuricea sp. (Plexauridae). Mar. Drugs 2012, 10, 2246–2253, doi:10.3390/md10102246.
  14. Seo, Y.; Rho, J.-R.; Cho, K.W.; Shin, J. Isolation of new steroidal hemiacetals from the gorgonian Euplexaura anastomosans. J. Nat. Prod. 1996, 59, 1196–1199, doi:10.1021/np960543f.
  15. Shin, J.; Seo, Y.; Cho, K.W.; Moon, S.-S.; Cho, Y.J. Euplexides A–E: Novel farnesylhydroquinone glycosides from the gorgonian Euplexaura anastomosans. J. Org. Chem. 1999, 64, 1853–1858, doi:10.1021/jo9817772.
  16. Seo, Y.; Rho, J.-R.; Cho, K.W.; Shin, J. New farnesylhydroquinone glycosides from the gorgonian Euplexaura anastomosans. Nat. Prod. Lett. 2001, 15, 81–87, doi:10.1080/10575630108041263.
  17. Komoda, Y.; Kanayasu, T.; Ishikawa, M. Prostaglandin F from the Japanese coastal gorgonian, Euplexaura erecta. Chem. Pharm. Bull. 1979, 27, 2491–2494, doi:10.1248/cpb.27.2491.
  18. Fusetani, N.; Matsunaga, S.; Konosu, S. Bioactive marine metabolites I. Isolation of guaiazulene from the gorgonian Euplexaura erecta. Experientia 1981, 37, 680–681, doi:10.1007/BF01967917.
  19. Kikuchi, H.; Tsukitani, Y.; Nakanishi, H.; Shimizu, I.; Saitoh, S.; Iguchi, K.; Yamada, Y. New butenolides from the gorgonian Euplexaura flava (Nutting). Chem. Lett. 1982, 11, 233–236.
  20. Sorek, H.; Rudi, A.; Benayahu, Y.; Ben-Califa, N.; Neumann, D.; Kashman, Y. Nuttingins A–F and malonganenones D–H, tetraprenylated alkaloids from the Tanzanian gorgonian Euplexaura nuttingi. J. Nat. Prod. 2007, 70, 1104–1109, doi:10.1021/np060642l.
  21. Fusetani, N.; Yasukawa, K.; Matsunaga, S.; Hashimoto, K. Bioactive marine metabolites XII. Moritoside, an inhibitor of the development of starfish embryo, from the gorgonian Euplexaura sp. Tetrahedron Lett. 1985, 26, 6449–6452.
  22. Deng, S.; Peng, S.; Li, F.; Tan, X.; Chen, J. A study on chemical constituents of South China Sea gorgonian Menella spinifera Kukenthal (I). Guangzhou Chem. 1993, 18(4), 44–47.
  23. Deng, S.; Li, F.; Peng, S.; Rao, Z.; Wu, H.; Xu, J. Chemical constituents of the South China Sea gorgonian Menella spinifera Kukenthal. Chin. J. Appl. Chem. 1997, 14(5), 80–82.
  24. Li, F.; Deng, S.; Rao, Z.; Wu, H.; Xu, J. Studies on chemical constituents of South China Sea gorgonian Menella spinifera Kukenthal (II). Guangzhou Chem. 1996, 21(3), 49–51.
  25. Zhang, W.; Guo, Y.-W.; Mollo, E.; Cimino, G. Menverins A–D, new highly oxygenated guaiane lactones from Hainan gorgonian Menella verrucosa (Brundin). Helv. Chim. Acta 2004, 87, 2919–2925, doi:10.1002/hlca.200490263.
  26. Zhang, W.; Huang, H.; Ding, Y.; Gavagnin, M.; Mollo, E.; Cimino, G.; Guo, Y.-W. Three new polyoxygenated steroids from two species of the South China Sea gorgonian Muricella flexuosa and Menella verrucosa Brundin. Helv. Chim. Acta 2006, 89, 813–820, doi:10.1002/hlca.200690073.
  27. Chai, X.-Y.; Sun, J.-F.; Tang, L.-Y.; Yang, X.-W.; Li, Y.-Q.; Huang, H.; Zhou, X.-F.; Yang, B.; Liu, Y. A novel cyclopentene derivative and a polyhydroxylated steroid from a South China Sea gorgonian Menella sp. Chem. Pharm. Bull. 2010, 58, 1391–1394, doi:10.1248/cpb.58.1391.
  28. Li, L.; Wang, C.-Y.; Huang, H.; Mollo, E.; Cimino, G.; Guo, Y.-W. Further highly oxygenated guaiane lactones from the South China Sea gorgonian Menella sp. Helv. Chim. Acta 2008, 91, 111–117, doi:10.1002/hlca.200890000.
  29. Chai, X.-Y.; Hu, J.; Huang, H.; Lei, H.; Chen, X.-Q.; Li, Y.-Q.; Sun, J.-F.; Dong, G.; Liu, Y.-H.; Liu, X.-D. Pregnane steroids from a gorgonian Menella sp. in South China Sea. J. Trop. Oceanogr. 2011, 30, 127–130.
  30. Kao, S.-Y.; Chang, Y.-C.; Su, J.-H.; Lu, M.-C.; Chen, Y.-H.; Sheu, J.-H.; Wen, Z.-H.; Wang, W.-H.; Kuo, Y.-H.; Hwang, T.-L.; et al. (–)-Hydroxylindestrenolide, a new sesquiterpenoid from a gorgonian coral Menella sp. (Plexauridae). Chem. Pharm. Bull. 2011, 59, 1048–1050, doi:10.1248/cpb.59.1048.
  31. Kao, S.-Y.; Su, J.-H.; Hwang, T.-L.; Sheu, J.-H.; Su, Y.-D.; Lin, C.-S.; Chang, Y.-C.; Wang, W.-H.; Fang, L.-S.; Sung, P.-J. Discovery of novel sesquiterpenoids from a gorgonian Menella sp. Tetrahedron 2011, 67, 7311–7315, doi:10.1016/j.tet.2011.07.043.
  32. Kao, S.-Y.; Su, J.-H.; Hwang, T.-L.; Sheu, J.-H.; Wen, Z.-H.; Wu, Y.-C.; Sung, P.-J. Menelloides C and D, new sesquiterpenoids from the gorgonian coral Menella sp. Mar. Drugs 2011, 9, 1534–1542, doi:10.3390/md9091534.
  33. Lee, C.-H.; Kao, C.-Y.; Kao, S.-Y.; Chang, C.-H.; Su, J.-H.; Hwang, T.-L.; Kuo, Y.-H.; Wen, Z.-H.; Sung, P.-J. Terpenoids from the octocorals Menella sp. (Plexauridae) and Lobophytum crassum (Alcyonacea). Mar. Drugs 2012, 10, 427–438, doi:10.3390/md10020427.
  34. Sung, P.-J.; Kao, S.-Y.; Kao, C.-Y.; Chang, Y.-C.; Chen, Y.-H.; Su, Y.-D. Seco-germacrane anhydride: Occurrence of a sesquiterpene lactone in the gorgonian coral Menella sp. (Plexauridae). Biochem. Syst. Ecol. 2012, 40, 53–55, doi:10.1016/j.bse.2011.10.012.
  35. Rocha, J.; Peixe, L.; Gomes, N.C.M.; Calado, R. Cnidarians as a source of new marine bioactive compounds—An overview of the last decade and future steps for bioprospecting. Mar. Drugs 2011, 9, 1860–1886, doi:10.3390/md9101860.
  36. Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.G.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep. 2012, 29, 144–222, doi:10.1039/c2np00090c.
  37. Berrue, F.; Kerr, R.G. Diterpenes from gorgonian corals. Nat. Prod. Rep. 2009, 26, 681–710, doi:10.1039/b821918b.
  • Samples Availability: Available from the authors.
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