Natural Bioactive Compounds from Marine-Derived Fungi
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marine drugs Review Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi Liming Jin, Chunshan Quan *, Xiyan Hou and Shengdi Fan College of Life Science, Dalian Nationalities University, No. 18, LiaoHe West Road, Dalian 116600, China; [email protected] (L.J.); [email protected] (X.H.); [email protected] (S.F.) * Correspondence: [email protected]; Tel.: +86-411-8765-6219; Fax: +86-411-8764-4496 Academic Editor: Vassilios Roussis Received: 27 January 2016; Accepted: 29 March 2016; Published: 22 April 2016 Abstract: In recent years, a considerable number of structurally unique metabolites with biological and pharmacological activities have been isolated from the marine-derived fungi, such as polyketides, alkaloids, peptides, lactones, terpenoids and steroids. Some of these compounds have anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, antibiotic and cytotoxic properties. This review partially summarizes the new bioactive compounds from marine-derived fungi with classification according to the sources of fungi and their biological activities. Those fungi found from 2014 to the present are discussed. Keywords: marine-derived fungi; fungal metabolites; bioactive compounds; natural products 1. Introduction The oceans, which cover more than 70% of the earth’s surface and more than 95% of the earth’s biosphere, harbor various marine organisms. Because of the special physical and chemical conditions in the marine environment, almost every class of marine organism displays a variety of molecules with structurally unique features. However, unlike the long historical medical uses of terrestrial plants, marine organisms have a shorter history in pharmacological application [1]. In recent years, a significant number of novel metabolites with pharmacological potential have been discovered from marine organisms, such as polyketides, alkaloids, peptides, proteins, lipids, shikimates, glycosides, isoprenoids and hybrids, which exhibit biological activity including anticancer, antitumor, antiproliferative, antimicrotubule, cytotoxic, photo protective, as well as antibiotic and antifouling properties [2]. Among them, marine microorganisms, such as bacteria, actinomycetes, fungi and cyanobacteria have attracted more attention as potential lead compound producers. In comparison to marine invertebrates, they are a renewable and a reproducible source, as they can be cultured and can even be envisaged as amazing microbial factories for natural products [3]. Previously, scientists always focused on actinomycetes for their abilities to produce antibiotics. In fact, many fungal metabolites in the pharmaceutical market indicates the potential of microorganisms as valuable sources of lead drugs, e.g., the antibiotic polyketide griseofulvin (Likuden M®), the antibacterial terpenoid fusidic acid (Fucidine®), semi-synthetic or synthetic penicillins and cephalosporins, macrolides, statins as well as the ergot alkaloids such as ergotamine (Ergo-Kranit®)[4]. In 1949, the first secondary metabolite isolated from a marine-derived fungal strain, famous cephalosporin C, was produced by a culture of a Cephalosporium sp. isolated from the Sardinian coast. However, this was a more or less accidental discovery. Despite the discovery of such important drug from marine fungi, the number of bioactive natural products originated from marine fungi increased extremely slowly. It is only from the late 1980s that researchers have focused on marine-derived fungi. In fact, marine-derived fungi are very important sources for novel bioactive secondary metabolites that could potentially be used as Mar. Drugs 2016, 14, 76; doi:10.3390/md14040076 www.mdpi.com/journal/marinedrugs Mar. Drugs 2016, 14, 76 2 of 25 Mar.important Drugs 2016 sources, 14, 76 for novel bioactive secondary metabolites that could potentially be used as drugs.2 of 25 Blunt et al., mentioned that marine‐derived fungi have a greater proportion of marine natural drugs.compoundsBlunt etwith al., mentionedmore desirable that marine-derived oral‐bioavailability fungi have and a greaterphysico proportion‐chemical ofproperties marine natural with compoundsmolecular weight with more (MW) desirable < 400 and oral-bioavailability clogP (calculated and octanol physico-chemical‐water logP) properties< 4 [5]. Compounds with molecular that weightmeet these(MW) criteria < 400 andcan clog suggestP (calculated the optimum octanol-water combinations logP) < for 4 [5 ].potential Compounds pharmaceuticals that meet these [5]. criteriaCurrently, can thousands suggest the of optimum structurally combinations unique and for biologically potential pharmaceuticals active compounds [5]. Currently, have been thousands reported offrom structurally marine fungi. unique and biologically active compounds have been reported from marine fungi. According to a classical definition,definition, marine fungi are divided intointo obligateobligate marinemarine fungi and facultative marine fungi [6]. [6]. In fact, marine fungi often live as symbionts in algae, mangrove, coral, sea anemone,anemone, starfish,starfish, seasea urchin,urchin, seagrass,seagrass, and,and, especially,especially, sponges.sponges. Collection of marine fungifungi usually requires the collection of the host or supportingsupporting material (e.g., algae, marine invertebrates, sediment or water, andand eveneven driftwood).driftwood). Herein, a neutral term “marine-derived“marine‐derived fungi” was used, whichwhich includesincludes any any fungal fungal strain strain obtained obtained from from marine marine environment environment using using cultivation cultivation techniques techniques with “marine”with “marine” media, whichmedia, do which not differentiate do not betweendifferentiate facultative between marine facultative strains and marine contaminants strains fromand terrestrialcontaminants habitats. from terrestrial habitats. The aim of thisthis reviewreview isis toto givegive anan overviewoverview onon secondarysecondary metabolitesmetabolites fromfrom marine-derivedmarine‐derived fungi and theirtheir biologicalbiological activities,activities, focusing on thethe periodperiod fromfrom 20142014 toto thethe present.present. In similarsimilar published reviews, assignments of a given metabolite to a certain category were generally based on structural considerations. It It is is obvious that classifications classifications of the enormous structural diversity of marine fungal-derivedfungal‐derived metabolites metabolites are are different different in in various various literature literature reports, reports, which which only only represents represents the authors’the authors’ personal personal judgments. judgments. In this In article, this article, these metabolitesthese metabolites were classified were classified according according to the sources to the ofsources marine of fungi. marine fungi. 2. Metabolites Metabolites from from Marine Marine-Derived‐Derived Fungi Fungi 2.1. Marine Animals 2.1.1. Sponge Two newnew 4-hydroxy-2-pyridone4‐hydroxy‐2‐pyridone alkaloids, arthpyrones (1–2), were isolated from thethe fungusfungus Arthrinium arundinis ZSDS1ZSDS1-F3,‐F3, which which obtained obtained from from sponge sponge (Xisha (Xisha Islands, Islands, China). China). Compounds Compounds 1 1andand 2 2hadhad signi significantficant inin vitro vitro cytotoxicitiescytotoxicities against against the the K562, K562, A549, A549, Huh Huh-7,‐7, H1975, MCF MCF-7,‐7, U937, BGC823, HL60,HL60, Hela Hela and and MOLT-4 MOLT cell‐4 lines,cell withlines, IC with50 values IC50 rangingvalues fromranging 0.24 tofrom 45 µ0.24M. Furthermore, to 45 μM. compoundFurthermore,2 displayed compound significant 2 displayed AchE significant inhibitory AchE activity inhibitory (IC50 =activity 0.81 µ M),(IC50 whereas = 0.81 μ compoundM), whereas1 showedcompound modest 1 showed activity modest (IC50 activity= 47 µM) (IC (Figure50 = 471 μ)[M)7]. (Figure 1) [7]. Figure 1. Structures of compounds 1–2. Figure 1. Structures of compounds 1–2. Chemical examination of the solid culture of the endophytic fungus Stachybotrys chartarum Stachybotrys chartarum isolatedChemical from the examination sponge Niphates of the recondita solid culture (Weizhou of the Island endophytic in Beibuwan fungus Bay, Guangxi Province of isolatedChina) resulted from the in sponge the isolationNiphates of reconditaseven new(Weizhou phenylspirodrimanes, Island in Beibuwan named Bay, chartarlactams Guangxi Province (3–9). ofCompounds China) resulted 3–9 exhibited in the isolation potent lipid of seven‐lowering new phenylspirodrimanes,effects in HepG2 cells in named a dose chartarlactams of 10 μM (Figure (3– 92)). µ Compounds[8]. 3–9 exhibited potent lipid-lowering effects in HepG2 cells in a dose of 10 M (Figure2)[ 8]. Mar. Drugs 2016,, 14,, 76 76 3 of 25 Mar. Drugs 2016, 14, 76 3 of 25 O O HO HO O HO NH NH HO ONH NH HO HO HO HO NH NH NH NH O O O O O HO O O O HO O O O HO AcO HO H H H H O HO AcO HO H H H H 3 45 6 3 45 6 HO HO O O H O OH O HO O H OH N-CH CH OH OH O O HO 2 2 HO O O OH N-CH2CH2OH NH HO HO OHO NH NH O OH HO NH O O O OH O O O HN OH O HN O HO HO HO O HO H HO H HO H H H H 7 8 9 7 8 9 Figure 2. Structures of compounds 3–9. FigureFigure 2.2. Structures of of compounds compounds 33––99. TheThe extract extract of of a astrain strain of of Aspergillus Aspergillus versicolor MF359MF359 (from(from the the sponge sponge of of Hymeniacidon Hymeniacidon perleve perleve, , BohaiBohaiThe Sea, Sea, extract China) China) of yielded ayielded strain one one of Aspergillusnew new secondarysecondary