A review of chemistry and biological activities of the Indonesian Octocorallia

Article history: Received on: 28/06/2016 Accepted on: 23/08/2016 Available online: 30/05/2017 Marine invertebrates are known to produce secondary metabolites that may have potential as new drug candidates. Numerous chemical studies have shown that sponges are a rich source of marine bioactive compounds. However, recent studies demonstrate that octocorals also produce secondary metabolites with promising pharmacological activities. In this paper, we report on the chemical and biological activities of the Indonesian octocorals, particularly soft corals, gorgonians and sea pens. Octocorals from the Ind onesian coasts have been demonstrated to contain a wide variety of compounds including steroids, sesquiterpenes and diterpenes. Cembranoid diterpenes have been largely founds in gorgonian and soft corals and they are believed to function as chemical defenses. Anti-inflammatory, antimicrobial, cytotoxic to antitumor have been disclosed for members of the cembranoid class.


INTRODUCTION
Marine organisms are an important source of new bioactive molecules; thus the scientific community worldwide is focusing its efforts on the isolation and characterization of biologically active natural products (Almeida et al., 2014).Since the early days of marine natural products research in the 1960s, sponges have yielded the largest number of new metabolites reported per year compared to any other plant or animal phylum known from the marine environment (Edaba and Proksch, 2012).However, with the development of new methods in analytical technology, spectroscopy, and high-throughput screening, the bioprospecting potential of cnidarians as they have also produced secondary metabolites with promising pharmacological activities (Molinski et al., 2009).A total of 3244 marine natural products was described from this phylum alone between 1990 and 2011, which shows the importance of cnidarians for marine natural product research (Rocha et al., 2015).
The phylum Cnidarian is a large, diverse and ecologically important group of marine invertebrates that are divided into five classes: Anthozoa, Hydrozoa, Cubozoa, Straurozoa and Chyphozoa and it contains over 11000 species, 7500 of them belonging to the class Anthozoa (Rocha et al., 2011;Daly et al., 2007).From the 3244 new compounds yielded by marine Cnidarians since 1990, 99% were discovered within Anthozoa.The remaining 1% is associated with species from Hydrozoa (Rocha et al., 2015).Anthozoa is divided into the subclasses Hexacorallia and Octocorallia, each one further separated into multiple orders.Octocorals comprise soft corals, sea pens and gorgonians, with eight tentacles and eight internal mesenteries that exhibit less variation in polyp morphology than hexacorals (Almeida et al., 2014;Rocha et al., 2011;McFadden et al., 2010).Octocorallia comprise approximately 3200 species of soft corals (Alcyonacea) found in all marine environments and 94% of new compounds from cnidarians were discovered from soft corals or Alcyonacea (Rocha et al., 2015).With all of these compounds, soft corals, or alcyonacea, proved to be the most promising source of compounds for pharmaceutical use.Terpenoid chemistry predominates across the Octocorallia class.
Sesquiterpenes and diterpenes are the most common terpenes isolated from Octocorallia.Numerous ecological studies have shown that to survive in the complicated marine environment, most octocorals produce diterpenes compounds, and these compounds are generally believed to function as chemical defenses.Several bioactivities including anti-inflammatory (Putra et al., 2012;Kapojos et al., 2010), antimicrobial (Wang et al., 2009), cytotoxic (Rodr guezet al., 1998;Fu et al., 1999), antitumor (Chen et al., 2011) have been isolated from members of the terpenoid class of Octocorallia.Since 1997-2014, more than 22 publications have reported on the bioactive compounds from Indonesian octocorallia such as sea pens, soft corals and gorgonians.Soft corals are the dominant reef-dwelling octocorals in the Indo-Pacific regions including Indonesia.Almost 99% of new marine natural products from Indonesian octcorals were collected from soft corals.In this review we report the marine compounds isolated from octocorals from Indonesia, specifically focusing on their structures and biological activities.

Soft corals
Soft corals are rich sources of secondary metabolites, particularly diterpenoids, sesquiterpenoid and steroids.The bioactive compounds in eight species of Indonesian soft corals such as Sinularia sp, Lobophytum sp, Cladiella sp, Xenia sp, Sarcophyton sp, Nephthea sp and Minabea sp, have been reported.Handayani and colleagues isolated two new oxygenated sesquiterpenes, hydroxycolorenone (1) and methoxycolorenone(2), and the known sesquiterpene, (+)-cyclocolorenone (3) from Nephthea chabrolii collected by snorkelling off the shores of Sinyary Island of West Sumatera (Handayani et al., 1997).Compound 1 exhibited insecticidal activity towards neonate larvae of the polyphagous pest insect Spodoptera littoralis, with an EC 50 of 8.8 ppm and LC 50 of 453 ppm, when incorporated in an artificial diet and offered to larvae in a chronic feeding bioassay.
Kapojos et al. reported two unusual cembranoids, sarcofuranocembrenolides A (21) and B ( 22), together with five known cembranoids named 5-epi-sinuleptolide (23),24, lobohedleolide( 25 Compound 29 exhibited moderate cytotoxicity toward CCRF-CEM tumor cells and this compound displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils.The cytotoxicity of metabolites 30-34 toward a limited panel of tumor cell lines, including DLD-1, HL-60, CCRF-CEM (human T-cell acute lymphoblastic leukemia), and P388D1 cells was evaluated.The results showed that cladieunicellins B (31) and E (34) exhibited significant cytotoxicity against DLD-1 and HL-60 cells.Compound 32 displayed a significant inhibitory effect against superoxide anion generation by human neutrophils.Compound 36 displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils at a concentration of 10 mg/mL.Similarly, from the same university, Tai et al. found two novel eunicellin-based diterpenoids, cladielloides C (37) and D (38) (Tai et al., 2011).

CONCLUSION
Marine invertebrates, which are plentiful in the Indo-Pacific regions including Indonesia, are rich in secondary metabolites and are becoming targets for the continuing search for bioactive compounds.The new metabolites from Indonesian marine organisms were mainly isolated from sponges.Octocorals are also being studied with promising results for secondary metabolites.Soft corals are the dominant reef dwelling octocorals in Indonesia.Since 1997-2014, more than 20 publications have reported on the bioactive compounds from Indonesian soft corals such as Cladiella sp., Lobophytum sp. and Sinularia sp.(Putra and Murniasih, 2016).
The discovery of novel compounds from Indonesian sea pens and gorgonians is much rarer, as indicated by the fact that until now only three publications have described novel compounds from them.Terpenes and sterols represented the two main chemical classes of compounds discovered from Indonesian marine organisms.