Metabolites from Marine Microorganisms, Micro, and Macroalgae: Immense Scope for Pharmacology
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marine drugs Review Metabolites from Marine Microorganisms, Micro, and Macroalgae: Immense Scope for Pharmacology Noora Barzkar 1,* , Saeid Tamadoni Jahromi 2,*, Hadi Bolooki Poorsaheli 3,4 and Fabio Vianello 5 1 Department of Marine Biology, Faculty of Marine Science and Technology, University of Hormozgan, Bandar Abbas 74576, Iran 2 Persian Gulf and Oman Sea Ecology Research Center, Iranian Fisheries Sciences Research Institute, Agricultural Research Education and Extension Organization (AREEO), Bandar Abbas 93165, Iran 3 Road, Housing & Urban Development Research Center (BHRC), Persian Gulf Branch, Bandar Abbas 93144, Iran 4 Department of Engineering, Islamic Azad University, Bandar Abbas 1696, Iran 5 Department of Comparative Biomedicine and Food Science, University of Padua, viale dell’Università 16, Legnaro 35020, Italy * Correspondence: [email protected] or [email protected] (N.B); [email protected] (S.T.J.) Received: 16 June 2019; Accepted: 27 July 2019; Published: 8 August 2019 Abstract: Marine organisms produce a large array of natural products with relevance in drug discovery. These compounds have biological activities such as antioxidant, antibacterial, antitumor, antivirus, anticoagulant, anti-inflammatory, antihypertensive, antidiabetic, and so forth. Consequently, several of the metabolites have made it to the advanced stages of clinical trials, and a few of them are commercially available. In this review, novel information on natural products isolated from marine microorganisms, microalgae, and macroalgae are presented. Given due research impetus, these marine metabolites might emerge as a new wave of promising drugs. Keywords: marine microorganisms; natural products; pharmaceutical potential; bacteria; microalgae; macroalgae 1. Introduction Oceans cover about 70% of the earth’s surface, serving as the habitat of a great diversity of organisms [1]. These organisms produce numerous metabolic products. Especially, lower organisms elaborate a multitude of secondary metabolites as signaling molecules for “defense and offense”. These compounds, which belong to diverse chemical classes, can act as potential therapeutics for healthcare [2]. In the past decades, several promising therapeutics have been extracted from bacteria, fungi, corals, micro- and macroalgae, gorgonians, sponges, nudibranchs, bryozoans, sea cucumbers, tunicates, and sea hares, among other marine organisms [3]. Considerable efforts have been directed towards the isolation of these compounds, and at the moment, more than 10,000 natural products (NPs) of potential biotechnological interest have been isolated [4]. The present review reports on the most promising bioactive compounds of marine origin, emphasizing their pharmaceutical potential. 2. Bioactive NPs from Marine Bacteria and Fungi In the marine environment, bacteria and fungi are pervasive. In the past decades, the number of reported bioactive compounds derived from marine bacteria and fungi has steadily increased [5]. Marine bacteria produce a large repertoire of secondary metabolites to survive in the hostile oceanic conditions. Among others, thermophilic and archaea bacteria elaborate thermostable enzymes which belong to diverse classes [1,6]. Mar. Drugs 2019, 17, 464; doi:10.3390/md17080464 www.mdpi.com/journal/marinedrugs Mar. Drugs 2019, 17, 2 of 29 Mar.conditions. Drugs 2019 Among, 17, 464 others, thermophilic and archaea bacteria elaborate thermostable enzymes which2 of 29 belong to diverse classes [1,6]. 2.1. Antibiotic Activity The myxomycetes Lycogala epidendrum produces halogenated bisindolebisindole pyrrole derivatives (Lynamicins A–E)A–E) (Figure (Figure1A–D) 1A–D) with antibacterialwith antibacterial activityagainst activityEnterococcus against faecalisEnterococcus, Staphylococcus faecalis, epidermidisStaphylococcus, and epidermidisStaphylococcus, and aureus Staphylococcus.Efficacy against aureus these. Efficacy pathogens against suggests these pathogens the potential suggests application the ofpotential these compounds application forof these the treatment compounds of nosocomialfor the treatment infections of nosocomial [7]. Similarly, infections a bacterium [7]. Similarly, isolated a frombacterium the sea isolated grass Thalassiafrom the producessea grass Thalassia a highly brominatedproduces a highly pyrrole brominated antibiotic [pyrrole8]. The crudeantibiotic extract [8]. ofTheNocardia crude extractsp. strain, of Nocardia isolated sp. from strain, the isolated marine redfrom marine the marine alga Laurenicared marine spectabilis, alga Laurenicaproduces spectabilis, active compoundsproduces active against compounds bacterial against and fungal bacteria pathogensl and fungal [9]. The pathogens eggs of the[9]. orientalThe eggs shrimp of thePalaemon oriental macrodactylusshrimp Palaemonharbor macrodactylus bacterial epibionts harbor bacterial with antifungal epibionts potential with antifungal towards thepotential pathogenic towards fungus the Lagenidiumpathogenic callinectesfungus Lagenidium[10]. Likewise, callinectes marine [10]. fungi Likewise, have been marine studied fungi for have their been bioactive studied compounds for their andbioactive they havecompounds proven toand be they a valuable have proven source ofto antibacterial, be a valuable antibiotic, source of antifungal, antibacterial, and anticancerantibiotic, compoundsantifungal, and [11 ].anticancer A marine compoundsAspergillus [11].sp. fungusA marine was Aspergillus isolated from sp. fungus the large was marine isolated brown from alga the Sargassumlarge marine horneri, brownand it producesalga Sargassum a polyoxygenated horneri, and decalin, it produces dehydroxychlorofusarielin a polyoxygenated B (Figure decalin,1E), whichdehydroxychlorofusarielin has demonstrated antibacterial B (Figure activity1E), which against has methicillin-resistantdemonstrated antibacterial and multidrug-resistant activity against (MDR)methicillin-resistantS. aureus [12]. and Another multidrug-resistant fungal Aspergillus (MDR)sp. strain, S. aureus isolated [12]. fromAnother a sea fungal fan (Alcyonacea Aspergillus), was sp. foundstrain, toisolated produce from antibacterial a sea fan (Alcyonacea compounds), was against foundS. to aureus produceATCC anti 25923bacterial and compounds methicillin-resistant against S. S.aureus aureus ATCC[13]. 25923 and methicillin-resistant S. aureus [13]. Figure 1. ChemicalChemical structure structure of of marine marine natural natural compou compoundsnds isolated isolated from from marine marine microorganisms. microorganisms. (A) (A)Lynamicin Lynamicin E; ( E;B) (B)Lynamicin Lynamicin B; B;(C) (C) Lynamicin Lynamicin A; A; (D (D)) Lynamicin Lynamicin D; D; (E (E)) Dehydroxychlorofusarielin Dehydroxychlorofusarielin B; B; (F)(F) AquastatinAquastatin A;A; (G)(G) Thiocoraline;Thiocoraline; (H)(H) PestalotiopsonePestalotiopsone F;F; (I)(I) AnhydrofulvicAnhydrofulvic acid; acid; (J) (J) Citromycetin. Citromycetin. 2.2. Anticancer Activity Besides antibiotics, antibiotics, marine marine microorganisms microorganisms are are also also a source a source of anticancer of anticancer principles. principles. The Thebacterium bacterium MicromonosporaMicromonospora sp. sp.produces produces thiocoraline thiocoraline (Figure (Figure 1G),1G), a a depsipeptide which inhibitsinhibits cellular DNA polymerase-αα.. This substance has been applied for the treatment treatment of cancer in preclinical preclinical research [[14].14]. An unidentifiedunidentified fungus of the PleosporalesPleosporales order (strain CRIF2) produces several compounds showing weak cytotoxic activity against tumor cell lines [[15].15]. A Pestalotiopsis spsp.. fungus, fungus, isolated from the leaves of Rhizophora mucronata, produces a chromone, namely, pestalotiopsonepestalotiopsone F (Figure1 1H),H),which which displays displays cytotoxic cytotoxic activity activity against against L5178Y L5178Y murine murine cancer cancer cells cells [ 16[16].]. Mar. Drugs 2019, 17, 464 3 of 29 2.3. Antidiabetic Activity Diabetes mellitus (or diabetes) is a debilitating and often life-threatening disorder that is prevalent worldwide, and the number of patients is significantly increasing [17]. Marine fungi have been screened for possible antidiabetic compounds [18]. The Cosmospora sp. SF-5060 fungus produces aquastatin A (Figure1F), a secondary metabolite which inhibits protein tyrosine phosphatases 1B (PTP1B) with an effective concentration (EC50) value of 0.19 µM. As PTP1B regulates insulin signaling and leptin receptor, aquastatin A might find an application in diabetes management [18]. Another marine fungus, Penicillium sp. JF-55, produces methylethylketone, which exerts inhibitory action on PTP1B as well. Other substances obtained from marine fungi are penstyrylpyrone, anhydrofulvic acid (Figure1I), and citromycetin (Figure1J), all displaying inhibitory actions of PTP1B with IC 50 values in the micromolar range [19]. Generally, marine bacteria and fungi species survive under hostile conditions, for example, high shear stress, high salinity, high light intensity, and low temperatures, which result in the elaboration of a large array of fascinating and structurally complex molecules. In Table1, some of the bioactive compounds produced by marine fungi and bacteria are listed. Mar. Drugs 2019Mar., Drugs17, 464 2019, 17, 4 of 29 4 of 29 Mar. Drugs 20192019,, 1717,, 44 ofof 2929 Table 1. Structure and biological activity of some novel marine microorganisms’ natural compounds. TableTable 1. Structure1. Structure and biological biological activity