Statistical research on marine natural products based on data obtained between 1985 and 2008

Since the 1960s, more than 20,000 compounds were discovered from marine organisms. In this paper we performed a quantitative analysis for the novel marine natural products reported between 1985 and 2008. The data was extracted mainly from the reviews of Faulkner and Blunt [1-26]. The organisms producing these marine natural products are divided into three major biological classes: marine microorganisms (including phytoplankton), marine algae and marine invertebrate. The marine natural products are divided into seven classes based on their chemical structure: terpenoids, steroids (including steroidal saponins), alkaloids, ethers (including ketals), phenols (including quinones), strigolactones, and peptides. The distribution and the temporal trend of these classes (biological classes and chemical structure classes) were investigated. We hope this article provides a comprehensive perspective on the research of marine natural products.     

Drugs and Cosmetics from the Sea

The marine environment is a rich source of both biological and chemical diversity. This diversity has been the source of unique chemical compounds with the potential for industrial development as pharmaceuticals, cosmetics, nutritional supplements, molecular probes, fine chemicals and agrochemicals. In recent years, a significant number of novel metabolites with potent pharmacological properties has been discovered from the marine organisms. Although there are only a few marine-derived products currently on the market, several robust new compounds derived from marine natural products are now in the clinical pipeline, with more clinical development. While the marine world offers an extremely rich resource for novel compounds, it also represents a great challenge that requires inputs from various scientific areas to bring the marine chemical diversity up to its therapeutic potential.     

Screening of Marine Bioactive Antimicrobial Compounds for Plant Pathogens

Plant diseases have been threatening food production. Controlling plant pathogens has become an important strategy to ensure food security. Although chemical control is an effective disease control strategy, its application is limited by many problems, such as environmental impact and pathogen resistance. In order to overcome these problems, it is necessary to develop more chemical reagents with new functional mechanisms. Due to their special living environment, marine organisms have produced a variety of bioactive compounds with novel structures, which have the potential to develop new fungicides. In the past two decades, screening marine bioactive compounds to inhibit plant pathogens has been a hot topic. In this review, we summarize the screening methods of marine active substances from plant pathogens, the identification of marine active substances from different sources, and the structure and antibacterial mechanism of marine active natural products. Finally, the application prospect of marine bioactive substances in plant disease control was prospected.     

Marine polysaccharides: a source of bioactive molecules for cell therapy and tissue engineering

The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications.     

Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.     

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.     

Structures and Biological Activities of Diketopiperazines from Marine Organisms: A Review

Diketopiperazines are potential structures with extensive biological functions, which have attracted much attention of natural product researchers for a long time. These compounds possess a stable six-membered ring, which is an important pharmacophore. The marine organisms have especially been proven to be a wide source for discovering diketopiperazine derivatives. In recent years, more and more interesting bioactive diketopiperazines had been found from various marine habitats. This review article is focused on the new 2,5-diketopiperazines derived from marine organisms (sponges and microorganisms) reported from the secondary half-year of 2014 to the first half of the year of 2021. We will comment their chemical structures, biological activities and sources. The objective is to assess the merit of these compounds for further study in the field of drug discovery.     

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.     

Sponges and Their Symbionts as a Source of Valuable Compounds in Cosmeceutical Field

In the last decades, the marine environment was discovered as a huge reservoir of novel bioactive compounds, useful for medicinal treatments improving human health and well-being. Among several marine organisms exhibiting biotechnological potential, sponges were highlighted as one of the most interesting phyla according to a wide literature describing new molecules every year. Not surprisingly, the first marine drugs approved for medical purposes were isolated from a marine sponge and are now used as anti-cancer and anti-viral agents. In most cases, experimental evidence reported that very often associated and/or symbiotic communities produced these bioactive compounds for a mutual benefit. Nowadays, beauty treatments are formulated taking advantage of the beneficial properties exerted by marine novel compounds. In fact, several biological activities suitable for cosmetic treatments were recorded, such as anti-oxidant, anti-aging, skin whitening, and emulsifying activities, among others. Here, we collected and discussed several scientific contributions reporting the cosmeceutical potential of marine sponge symbionts, which were exclusively represented by fungi and bacteria. Bioactive compounds specifically indicated as products of the sponge metabolism were also included. However, the origin of sponge metabolites is dubious, and the role of the associated biota cannot be excluded, considering that the isolation of symbionts represents a hard challenge due to their uncultivable features.     

Biomaterials and Bioactive Natural Products from Marine Invertebrates: From Basic Research to Innovative Applications

Aquatic invertebrates are a major source of biomaterials and bioactive natural products that can find applications as pharmaceutics, nutraceutics, cosmetics, antibiotics, antifouling products and biomaterials. Symbiotic microorganisms are often the real producers of many secondary metabolites initially isolated from marine invertebrates; however, a certain number of them are actually synthesized by the macro-organisms. In this review, we analysed the literature of the years 2010–2019 on natural products (bioactive molecules and biomaterials) from the main phyla of marine invertebrates explored so far, including sponges, cnidarians, molluscs, echinoderms and ascidians, and present relevant examples of natural products of interest to public and private stakeholders. We also describe omics tools that have been more relevant in identifying and understanding mechanisms and processes underlying the biosynthesis of secondary metabolites in marine invertebrates. Since there is increasing attention on finding new solutions for a sustainable large-scale supply of bioactive compounds, we propose that a possible improvement in the biodiscovery pipeline might also come from the study and utilization of aquatic invertebrate stem cells.     

Chemical Diversity and Biological Properties of Secondary Metabolites from Sea Hares of Aplysia Genus

The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a successful phyla in the discovery of new marine natural products (MNPs). Over a 50-year period from 1963, 116 genera of mollusks contributed innumerous compounds, Aplysia being the most studied genus by MNP chemists. This genus includes 36 valid species and should be distinguished from all mollusks as it yielded numerous new natural products. Aplysia sea hares are herbivorous mollusks, which have been proven to be a rich source of secondary metabolites, mostly of dietary origin. The majority of secondary metabolites isolated from sea hares of the genus Aplysia are halogenated terpenes; however, these animals are also a source of compounds from other chemical classes, such as macrolides, sterols and alkaloids, often exhibiting cytotoxic, antibacterial, antifungal, antiviral and/or antifeedant activities. This review focuses on the diverse structural classes of secondary metabolites found in Aplysia spp., including several compounds with pronounced biological properties.     

Genus Nocardiopsis: A Prolific Producer of Natural Products

Actinomycetes are currently one of the major sources of bioactive secondary metabolites used for medicine development. Accumulating evidence has shown that Nocardiopsis, a key class of actinomycetes, has the ability to produce novel bioactive natural products. This review covers the sources, distribution, bioactivities, biosynthesis, and structural characteristics of compounds isolated from Nocardiopsis in the period between March 2018 and 2021. Our results reveal that 67% of Nocardiopsis-derived natural products are reported for the first time, and 73% of them are isolated from marine Nocardiopsis. The chemical structures of the Nocardiopsis-derived compounds have diverse skeletons, concentrating on the categories of polyketides, peptides, terphenyls, and alkaloids. Almost 50% of the natural products isolated from Nocardiopsis have been discovered to display various bioactivities. These results fully demonstrate the great potential of the genus Nocardiopsis to produce novel bioactive secondary metabolites that may serve as a structural foundation for the development of novel drugs.     

Recent Advances and Applications of Experimental Technologies in Marine Natural Product Research

Marine natural products are a rich source of novel and biologically active compounds. The number of identified marine natural compounds has grown 20% over the last five years from 2009 to 2013. Several challenges, including sample collection and structure elucidation, have limited the development of this research field. Nonetheless, new approaches, such as sampling strategies for organisms from extreme ocean environments, nanoscale NMR and computational chemistry for structural determination, are now available to overcome the barriers. In this review, we highlight the experimental technology innovations in the field of marine natural products, which in our view will lead to the development of many new drugs in the future.     

Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.     

Natural Polypropionates in 1999–2020: An Overview of Chemical and Biological Diversity

Natural polypropionates (PPs) are a large subgroup of polyketides with diverse structural features and bioactivities. Most of the PPs are discovered from marine organisms including mollusks, fungi and actinomycetes, while some of them are also isolated from terrestrial resources. An increasing number of studies about PPs have been carried out in the past two decades and an updated review is needed. In this current review, we summarize the chemical structures and biological activities of 164 natural PPs reported in 67 research papers from 1999 to 2020. The isolation, structural features and bioactivities of these PPs are discussed in detail. The chemical diversity, bioactive diversity, biodiversity and the relationship between chemical classes and the bioactivities are also concluded.     

Antitumor peptides from marine organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.     

Potential Anti-HPV and Related Cancer Agents from Marine Resources: An Overview

Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail.     

Recent Discoveries on Marine Organism Immunomodulatory Activities

Marine organisms have been shown to be a valuable source for biologically active compounds for the prevention and treatment of cancer, inflammation, immune system diseases, and other pathologies. The advantage of studying organisms collected in the marine environment lies in their great biodiversity and in the variety of chemical structures of marine natural products. Various studies have focused on marine organism compounds with potential pharmaceutical applications, for instance, as immunomodulators, to treat cancer and immune-mediated diseases. Modulation of the immune system is defined as any change in the immune response that can result in the induction, expression, amplification, or inhibition of any phase of the immune response. Studies very often focus on the effects of marine-derived compounds on macrophages, as well as lymphocytes, by analyzing the release of mediators (cytokines) by using the immunological assay enzyme-linked immunosorbent assay (ELISA), Western blot, immunofluorescence, and real-time PCR. The main sources are fungi, bacteria, microalgae, macroalgae, sponges, mollusks, corals, and fishes. This review is focused on the marine-derived molecules discovered in the last three years as potential immunomodulatory drugs.     

Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation

Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.