molecules Review A Brief Review on New Naturally Occurring Cembranoid Diterpene Derivatives from the Soft Corals of the Genera Sarcophyton, Sinularia, and Lobophytum Since 2016 Inna Glibka Rodrigues 1, Maria Graça Miguel 1 and Wissem Mnif 2,3,* 1 Faculdade de Ciências e Tecnologia, Departamento de Química e Farmácia, Universidade do Algarve, Edifício 8, MeditBio, Campus de Gambelas, 8005-139 Faro, Portugal; [email protected] (I.G.R.); [email protected] (M.G.M.) 2 Department of Chemistry, Faculty of Sciences and Arts in Balgarn, University of Bisha, Bisha 61922, P.O. BOX 199, Saudi Arabia 3 Univ. Manouba, ISBST, BVBGR-LR11ES31, Biotechpole Sidi Thabet, Ariana 2020, Tunisia * Correspondence: [email protected]; Tel.: +216-9894-7371 Received: 23 October 2018; Accepted: 10 January 2019; Published: 21 February 2019 Abstract: This work reviews the new isolated cembranoid derivatives from species of the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2018. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton than in those belonging to the genera Lobophytum or Sinularia. Beyond the chemical composition, the biological properties were also reviewed, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. In spite of the biological activities detected in almost all samples, there is a remarkable diversity in the results which may be attributed to the chemical variability that needs to be deepened in order to develop new molecules with potential application in medicine. Keywords: Sarcophyton; Sinularia; Lobophytum; anti-microbial; anti-inflammatory; anti-tumoral 1. Introduction The cembrane skeleton is isoprenoid and consists of a fourteen-membered carbocyclic ring with an isopropyl residue at position 1 and three methyl groups at positions 4, 8, and 12 (Figure1). The basic structure of this diterpene usually presents cyclic ether, lactone, or furan moieties around the macrocyclic ring. There are also cembranoids variants which contain a 12 or 13-membered carbon skeleton [1–3]. In nature, this class of diterpenoids has been found in marine invertebrates, lower and higher plants, insects (termites), and even paracloacal glands of Chinese male alligators (Alligator sinensis)[4,5]. Cembranoids from marine invertebrates are particularly isolated from soft corals of the genera Sinularia, Lobophytum, Eunicea, Clavularia, and Sarcophyton, and from the gorgonian octocorals, mainly of the genera Pseudopterogorgia, Leptogorgia, and Lophogorgia [1,6,7]. Soft corals (phylum, Cnidaria; class, Anthozoa; subclass, Octocorallia; order, Alcyonaceae; family, Alcyoniidae) have been the target of study since the nineteenth century. The subclass Octocorallia includes soft corals, gorgonians, and sea pens. Most soft corals belong to the order Alcyonacea that comprises several families, including Alcyoniidae. This family contains the genera Sarcophyton, Sinularia, and Lobophytum [8]. Soft corals are found in Indo Pacific reefs whereas Gorgonian octocorals Molecules 2019, 24, 781; doi:10.3390/molecules24040781 www.mdpi.com/journal/molecules MoleculesMolecules 20192018,, 2423,, 781x FOR PEER REVIEW 22 of of 3342 Sarcophyton, Sinularia, and Lobophytum [8]. Soft corals are found in Indo Pacific reefs whereas dominateGorgonian the octocorals biomass dominate in coral reefthe biomass environments in coral of reef the environments north-western of Atlanticthe north-western Ocean and Atlantic in the CaribbeanOcean and Seain the [7]. Caribbean Sea [7]. FigureFigure 1. 1.Cembrane Cembrane skeleton. skeleton. InIn nature,nature, cembranoidscembranoids maymay actact asas chemicalchemical defensedefense compoundscompounds againstagainst fishfish predators predators and/or and/or competingcompeting for reef organisms, bacteria, parasites, parasites, to to ensure ensure their their protection protection and and survivalsurvival [7,9]. [7,9]. MultipleMultiple inin vitro vitro biologicalbiological properties properties of ofcembranoids cembranoids of marine of marine origin origin have been have reported been reported such as suchanti-inflammatory, as anti-inflammatory, anti-tumoral, anti-tumoral, anti-bacterial, anti-bacterial, anti-viral, anti-viral, neuroprotective, neuroprotective, antiarthritic, antiarthritic, calcium- calcium-antagonistic,antagonistic, and cytotoxic and cytotoxic[9,10]. This [9, 10is ].the This first is step the for first the step in vivo for the assaysin vivo whichassays will which determine will determinewhether or whether not they or constitute not they constitutepotential therapeutic potential therapeutic agents agents. YangYang etet al. al. [10 [10]] review review all all the the metabolites metabolites of cembrane of cembrane diterpenes diterpenes either either from terrestrial from terrestrial or marine or organismsmarine organisms up to 2010. up Theyto 2010. were They divided were intodivided several into different several familiesdifferent according families according to the variety to the of ringvariety sizes, of ring oxidation sizes, patterns,oxidation and patterns, the respective and the re biologicalspective activities.biological Severalactivities. other Several reviews other have reviews been madehave been regarding made new regarding compounds new compounds and their biological and thei activities.r biological These activities compounds. These have compounds been isolated have frombeen isolated marine microorganismsfrom marine microorganisms and phytoplankton, and phytop green,lankton, brown green, and red brown algae, and sponges, red algae, cnidarians, sponges, bryozoans,cnidarians, mollusks,bryozoans, tunicates, mollusks, echinoderms, tunicates, echinoderms, mangroves and mangroves other intertidal and other plants, intertidal from 2013 plants, until 2017from [ 112013–14 until]. Marine 2017 invertebrates [11–14]. Marine isolated invertebrates from soft coralsisolated of thefrom genera soft coralsSinularia of ,theLobophytum genera Sinularia, Eunicea, andLobophytumSarcophyton, Euniceaare also, and included Sarcophyton in these are also reviews. included in these reviews. LiangLiang and Guo [15], [15], in in a a review review on on the the te terpenesrpenes from from the the soft soft coral coral of ofthe the genus genus SarcophytonSarcophyton (S. (elegansS. elegans, S., glaucumS. glaucum, S., ehrenbergiS. ehrenbergi, S., trocheliophorumS. trocheliophorum, S., molleS. molle, S., mililatensisS. mililatensis, S., crassocauleS. crassocaule, S., latumS. latum, S., S.cherbonnieri cherbonnieri, S., S.stolidotum stolidotum, S., S.tortuosum tortuosum, ,S.S. infundibuliforme infundibuliforme, ,S.S. flexuosum flexuosum, , S.S. solidum ,, and somesome undefinedundefined species)species) from differentdifferent geographicalgeographical origins,origins, reported 165 diterpenes,diterpenes, 29 biscembranoids, amongamong otherother terpeneterpene compounds,compounds, duringduring thethe periodperiod 1995–July1995–July 2011.2011. Some of thesethese compoundscompounds possessedpossessed biologicalbiological properties.properties. TheThe presentpresent workwork willwill review review the the new new cembranoid cembranoid diterpenes diterpenes isolated isolated from from species species belonging belonging to theto the family family Alcyoniidae, Alcyoniidae, which which contains contains the the genera generaSarcophyton Sarcophyton, Sinularia, Sinularia, and, andLobophytum Lobophytumas wellas well as theiras their biological biological properties, properties, since since 2016. 2016. For this For review, this review, only the onlyWeb the of ScienceWeb of wasScience used was as aused database as a fordatabase research for by research utilizing by the utilizing keywords the keywordscembrane, andcembranecembranoid, and cembranoid. 2.2. Chemical Structure ofof CembranoidsCembranoids fromfrom MarineMarine OriginOrigin AccordingAccording toto RodrRodríguezíguez et al.al. [[16],16], thethe cembranecembrane skeletonskeleton ofof marinemarine originorigin isis derivedderived fromfrom thethe cyclizationcyclization ofof geranylgeranylgeranylgeranyl pyrophosphate.pyrophosphate. This hypothesis is based on the fact that thethe doubledouble bondsbonds ofof thethe cembranecembrane skeletonskeleton havehave thethe geometrygeometry EE whichwhich isis observedobserved inin geranylgeraniol.geranylgeraniol. CembraneCembrane diterpenoidsditerpenoids havehave diversediverse structuralstructural variationsvariations withwith aa multitude of functional groups (lactone,(lactone, epoxide,epoxide, furan,furan, ester,ester, aldehyde,aldehyde, hydroxyl,hydroxyl, carboxylcarboxyl moieties)moieties) andand cyclizations,cyclizations, whichwhich permitpermit toto groupgroup them them in in several several families families [10 [10,17].,17]. According According to to the the review review of Yangof Yang et al. et [ 10al.], [10], the cembrane-typethe cembrane- diterpenoidstype diterpenoids may bemay classified be classified as depicted as depicted in Table in 1Table. 1. CembranolidesCembranolides possess possess a a 14-membered 14-membered carbocyclic carbocyclic nu nucleus,cleus, generally generally fused fused to a to5-,a 6-, 5-, 7-, 6-, or 7-,8- ormembered 8-membered lactone lactone ring. Furanocembranoids ring. Furanocembranoids possess possess a 14-membered a 14-membered carbocyclic carbocyclic nucleus as nucleus well as as a wellfuran as heterocycle.