Natural Products from Octocorals of the Genus Dendronephthya (Family Nephtheidae)

In this review, 170 natural substances, including steroid, diterpenoid, sesquiterpenoid, peptide, prostaglandin, base, chlorolipid, bicyclolactone, amide, piperazine, polyketide, glycerol, benzoic acid, glycyrrhetyl amino acid, hexitol, pentanoic acid, aminoethyl ester, octadecanone, alkaloid, and a 53-kD allergenic component from octocorals belonging to genus Dendronephthya, were listed. Some of these compounds displayed potential bioactivities.

Molecules 2020, 25, x FOR PEER REVIEW 2 of 25 [2] (Figure 1), subsequent studies over the past two decades have yielded a series of interesting secondary metabolites, particularly steroid metabolites. In this article, different types of compounds isolated from Dendronephthya spp., were summarized.

Dendronephthya griffini (Roxas, 1933)
Ten new steroids, griffinisterones A-I (56-64) and griffinipregnone (65) (Figure 9), were obtained from D. griffini specimens collected by a bottom trawl net at depths from 200 to 100 m at Taiwan Straight in December 2004 [61,62]. The structures of steroids 56-65 were determined by spectroscopic methods and the configuration of griffinisterone A (56) was further confirmed by a single-crystal X-ray diffraction analysis [61,62]. The absolute stereochemistry of griffinisterone E (60) was determined by the application of a modified phenylglycine methyl ester (PGME) method [61].

Dendronephthya nipponica (Utinomi, 1952)
A red soft-coral D. nipponica cause spiny lobster fisherman living along the coast of Miyazaki Prefecture, Japan to develop occupational allergies. In order to understand the allergic mechanism, a new 53-kD allergenic component (Den n 1) (87) was purified and the N-terminal amino of this allergen component was determined and identified as Asp-Asp-IIe-Asn-Arg-Tyr-Ala-Phe-Asp-Asn-Lys-IIe-Asn-Asp-Lys-Leu-Phe-Asp-His-Trp-Gln-Ser [83].

Dendronephthya nipponica (Utinomi, 1952)
A red soft-coral D. nipponica cause spiny lobster fisherman living along the coast of Miyazaki Prefecture, Japan to develop occupational allergies. In order to understand the allergic mechanism, a new 53-kD allergenic component (Den n 1) (87) was purified and the N-terminal amino of this allergen component was determined and identified as Asp-Asp-IIe-Asn-Arg-Tyr-Ala-Phe-Asp-Asn-Lys-IIe-Asn-Asp-Lys-Leu-Phe-Asp-His-Trp-Gln-Ser [83].
Molecules 2020, 25, x FOR PEER REVIEW 10 of 25 tory effects of this sterol-rich mixture was confirmed in an LPS-stimulated in vivo zebrafish model by the downregulation of NO, iNOS, COX-2, ROS production and cell death [85,86], and this sterol rich congener showed cytotoxicity toward HL-60 and MCF-7 cells with IC50 values of 25.27 and 22.81 µ g/mL, respectively [87].
Molecules 2020, 25, x FOR PEER REVIEW 10 of 25 tory effects of this sterol-rich mixture was confirmed in an LPS-stimulated in vivo zebrafish model by the downregulation of NO, iNOS, COX-2, ROS production and cell death [85,86], and this sterol rich congener showed cytotoxicity toward HL-60 and MCF-7 cells with IC50 values of 25.27 and 22.81 µ g/mL, respectively [87].

Dendronephthya spp.
Dendronephthya is a genus of octocoral belonging to the family Nephtheidae and there are over 250 described species in this genus. In 1990, Katrich and colleagues identified the correlation between the number of particular phospholipids (PhLs) and prostaglandins (PGs) that influenced the prostaglandin-like activities of the extracts from (1) Dendronephthya sp., collected in the region of the Great Barrier Reef, Australia and (2) Dendronephthya sp., collected in Vietnam [96].
An acetone extract from Dendronephthya sp., collected in 1990, off the Chichi-jima and Haha-jima

Dendronephthya spp.
Dendronephthya is a genus of octocoral belonging to the family Nephtheidae and there are over 250 described species in this genus. In 1990, Katrich and colleagues identified the correlation between the number of particular phospholipids (PhLs) and prostaglandins (PGs) that influenced the prostaglandin-like activities of the extracts from (1) Dendronephthya sp., collected in the region of the Great Barrier Reef, Australia and (2) Dendronephthya sp., collected in Vietnam [96].

Kawamata et al.
isolated an antifouling substance, trigonelline (109) (Figure 18), from Dendronephthya sp. collected at Chichijima Island in the Ogasawara Islands [102]. The structure of 109 was elucidated by spectroscopic methods and this compound showed the same level of settling-inhibitory activity against the acorn barnacle Balanus amphitrite larvae as CuSO 4 [102,103].  (Figure 5), β-sitosterol (stigmasta-5-en-3β-ol) (39) [48], and β-cholestanol (5α-cholestan-3βol) (107) [99] were identified and sterol 39 in this study [97] was found to contain 35% of a 24S epimer (clionasterol) (108) [100,101] (Figure 17). Sterol 39 had the highest antifouling activity among sterols 26, 39, and 107 [97]. Moreover, a fatty acid mixture, showing the presence of saturated and unsaturated fatty acids with a chain length of C12 to C22, being rich in C16 and C18 acids as active constituents in antifouling activity [97].  (Figure 18), from Dendronephthya sp. collected at Chichijima Island in the Ogasawara Islands [102]. The structure of 109 was elucidated by spectroscopic methods and this compound showed the same level of settlinginhibitory activity against the acorn barnacle Balanus amphitrite larvae as CuSO4 [102,103]. In 1999, the ethanol extract of two soft coral specimens Dendronephthya (Roxasia) sp. and Dendronephthya (Morchellana) sp., collected off the Gopalpur coast, Bay of Bengal, were found to display attachment inhibitory activity against the settlement of cyprids of barnacle Balanus amphitrite [104], and the extract was claimed to contain natural non-toxic antifouling agents, although no natural In 1999, the ethanol extract of two soft coral specimens Dendronephthya (Roxasia) sp. and Dendronephthya (Morchellana) sp., collected off the Gopalpur coast, Bay of Bengal, were found to display attachment inhibitory activity against the settlement of cyprids of barnacle Balanus amphitrite [104], and the extract was claimed to contain natural non-toxic antifouling agents, although no natural products was reported to be active components.

Conclusions
Ever since the seco-steroids, isogosterones A-D (1-4) were obtained from a specimen of the octocoral Dendronephthya collected off the Izu Peninsula, Japan [2], 170 interesting secondary metabolites, including 96 steroids (56.47%), 20 cembranes (11.76%), 11 sesquiterpenoids (6.47%), 11 amides (6.47%), 4 chlorolipids (2.35%), 4 bicyclic lactones (2.35%), 4 prostaglandins (2.35%), 4 bases (2.35%), 3 peptides (1.76%), 2 polyketides (1.18%), 2 ceramides (1.18%), 1 glycerol (0.59%), 1 glycyrrhetyl amino acid (0.59%), 1 benzoic acid (0.59%), 1 trigonelline (0.59%), 1 hexitol (0.59%), 1 pentanoic acid (0.59%), 1 octadecanone (0.59%), 1 aminoethyl ester (0.59%), and a 53-KD allergenic component (0.59%), were produced by Dendronephthya spp., and extensive biomedical activities, especially in cytotoxicity and anti-inflammatory activity, were related to these natural substances ( Figure 28). All the secondary metabolites from Dendronephthya spp., reported between 1999 and 2019 were obtained from the octocorals distributed in the Indo-Pacific Ocean and Red Sea. As more than 56% of the compounds obtained from the Dendronephthya genus are steroids, based on above findings, these results suggest that continuing the investigation of new steroid analogues with the potential bioactivities from this marine organism are worthwhile for further development. The octocoral Dendronephthya sp. had been transplanted to culturing tanks located in the National Museum of Marine Biology and Aquarium, Taiwan, for the extraction of additional natural products to establish a stable supply of bioactive material.  All the secondary metabolites from Dendronephthya spp., reported between 1999 and 2019 were obtained from the octocorals distributed in the Indo-Pacific Ocean and Red Sea. As more than 56% of the compounds obtained from the Dendronephthya genus are steroids, based on above findings, these results suggest that continuing the investigation of new steroid analogues with the potential bioactivities from this marine organism are worthwhile for further development. The octocoral Dendronephthya sp. had been transplanted to culturing tanks located in the National Museum of Marine Biology and Aquarium, Taiwan, for the extraction of additional natural products to establish a stable supply of bioactive material.