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1.
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources. 相似文献
2.
Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6. 相似文献
3.
F. Jerry Reen José A. Gutiérrez-Barranquero Alan D. W. Dobson Claire Adams Fergal O’Gara 《Marine drugs》2015,13(5):2924-2954
The vast oceans of the world, which comprise a huge variety of unique ecosystems, are emerging as a rich and relatively untapped source of novel bioactive compounds with invaluable biotechnological and pharmaceutical potential. Evidence accumulated over the last decade has revealed that the diversity of marine microorganisms is enormous with many thousands of bacterial species detected that were previously unknown. Associated with this diversity is the production of diverse repertoires of bioactive compounds ranging from peptides and enzymes to more complex secondary metabolites that have significant bioactivity and thus the potential to be exploited for innovative biotechnology. Here we review the discovery and functional potential of marine bioactive peptides such as lantibiotics, nanoantibiotics and peptidomimetics, which have received particular attention in recent years in light of their broad spectrum of bioactivity. The significance of marine peptides in cell-to-cell communication and how this may be exploited in the discovery of novel bioactivity is also explored. Finally, with the recent advances in bioinformatics and synthetic biology, it is becoming clear that the integration of these disciplines with genetic and biochemical characterization of the novel marine peptides, offers the most potential in the development of the next generation of societal solutions. 相似文献
4.
Francesco Margiotta Laura Micheli Clara Ciampi Carla Ghelardini J. Michael McIntosh Lorenzo Di Cesare Mannelli 《Marine drugs》2022,20(12)
Conus regius is a marine venomous mollusk of the Conus genus that captures its prey by injecting a rich cocktail of bioactive disulfide bond rich peptides called conotoxins. These peptides selectively target a broad range of ion channels, membrane receptors, transporters, and enzymes, making them valuable pharmacological tools and potential drug leads. C. regius-derived conotoxins are particularly attractive due to their marked potency and selectivity against specific nicotinic acetylcholine receptor subtypes, whose signalling is involved in pain, cognitive disorders, drug addiction, and cancer. However, the species-specific differences in sensitivity and the low stability and bioavailability of these conotoxins limit their clinical development as novel therapeutic agents for these disorders. Here, we give an overview of the main pharmacological features of the C. regius-derived conotoxins described so far, focusing on the molecular mechanisms underlying their potential therapeutic effects. Additionally, we describe adoptable chemical engineering solutions to improve their pharmacological properties for future potential clinical translation. 相似文献
5.
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. 相似文献
6.
Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt®; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 相似文献
7.
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. 相似文献
8.
Gary S. Caldwell 《Marine drugs》2009,7(3):367-400
Diatoms are one of the main primary producers in aquatic ecosystems and occupy a vital link in the transfer of photosynthetically-fixed carbon through aquatic food webs. Diatoms produce an array of biologically-active metabolites, many of which have been attributed as a form of chemical defence and may offer potential as candidate marine drugs. Of considerable interest are molecules belonging to the oxylipin family which are broadly disruptive to reproductive and developmental processes. The range of reproductive impacts includes; oocyte maturation; sperm motility; fertilization; embryogenesis and larval competence. Much of the observed bioactivity may be ascribed to disruption of intracellular calcium signalling, induction of cytoskeletal instability and promotion of apoptotic pathways. From an ecological perspective, the primary interest in diatom-oxylipins is in relation to the potential impact on energy flow in planktonic systems whereby the reproductive success of copepods (the main grazers of diatoms) is compromised. Much data exists providing evidence for and against diatom reproductive effects; however detailed knowledge of the physiological and molecular processes involved remains poor. This paper provides a review of the current state of knowledge of the mechanistic impacts of diatom-oxylipins on marine invertebrate reproduction and development. 相似文献
9.
Background: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. Method: 52,765 marine natural products were screened against PD-L1(PDBID: 6R3K). To identify natural compounds, a structure-based pharmacophore model was generated, following by virtual screening and molecular docking. Then, the absorption, distribution, metabolism, and excretion (ADME) test was carried out to select the most suitable compounds. Finally, molecular dynamics simulation was also performed to validate the binding property of the top compound. Results: Initially, 12 small marine molecules were screened based on the pharmacophore model. Then, two compounds were selected for further evaluation based on the molecular docking scores. After ADME and toxicity studies, molecule 51320 was selected for further verification. By molecular dynamics analysis, molecule 51320 maintains a stable conformation with the target protein, so it has the chance to become an inhibitor of PD-L1. Conclusions: Through structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET approaches, and molecular dynamics (MD) simulation, the marine natural compound 51320 can be used as a small molecule inhibitor of PD-L1. 相似文献
10.
Shimei Xiao Zhiqiang Wang Huanli Zhang Lei Zhao Qingran Chang Xiong Zhang Rui Yan Xiaodan Wu Yingxue Jin 《Marine drugs》2022,20(6)
The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly5 (compound 8) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca2+ concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound 8. Western blotting tests showed that compound 8 could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides. 相似文献
11.
Md. Tanvir Kabir Md. Sahab Uddin Philippe Jeandet Talha Bin Emran Saikat Mitra Ghadeer M. Albadrani Amany A. Sayed Mohamed M. Abdel-Daim Jesus Simal-Gandara 《Marine drugs》2021,19(5)
Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD. 相似文献
12.
The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs. 相似文献
13.
Thilina U. Jayawardena K. K. Asanka Sanjeewa D. P. Nagahawatta Hyo-Geun Lee Yu-An Lu A. P. J. P. Vaas D. T. U. Abeytunga C. M. Nanayakkara Dae-Sung Lee You-Jin Jeon 《Marine drugs》2020,18(12)
This study involves enzymatic extraction of fucoidan from Sargassum swartzii and further purification via ion-exchange chromatography. The chemical and molecular characteristics of isolated fucoidan is evaluated concerning its anti-inflammatory potential in RAW 264.7 macrophages under LPS induced conditions. Structural properties of fucoidan were assessed via FTIR and NMR spectroscopy. NO production stimulated by LPS was significantly declined by fucoidan. This was witnessed to be achieved via fucoidan acting on mediators such as iNOS and COX-2 including pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), with dose dependent down-regulation. Further, the effect is exhibited by the suppression of TLR mediated MyD88, IKK complex, ultimately hindering NF-κB and MAPK activation, proposing its therapeutic applications in inflammation related disorders. The research findings provide an insight in relation to the sustainable utilization of fucoidan from marine brown algae S. swartzii as a potent anti-inflammatory agent in the nutritional, pharmaceutical, and cosmeceutical sectors. 相似文献
14.
Tiago Leo Mingxun Wang Nathan Moss Ricardo da Silva Jon Sanders Sergey Nurk Alexey Gurevich Gregory Humphrey Raphael Reher Qiyun Zhu Pedro Belda-Ferre Evgenia Glukhov Syrena Whitner Kelsey L. Alexander Robert Rex Pavel Pevzner Pieter C. Dorrestein Rob Knight Nuno Bandeira William H. Gerwick Lena Gerwick 《Marine drugs》2021,19(1)
Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples. 相似文献
15.
Matrix metalloproteinases (MMPs) are a family of more than twenty five secreted and membrane-bound zinc-endopeptidases which can degrade extracellular matrix (ECM) components. They also play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation. Up to present, more than 20,000 new compounds have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. Eventhough the quantity of marine derived MMPIs is less when compare with the MMPIs derived from terrestrial materials, huge potential for bioactivity of these marine derived MMPIs has lead to large number of researches. Saccharoids, flavonoids and polyphones, fatty acids are the most important groups of MMPIs derived from marine natural products. In this review we focus on the progress of MMPIs from marine natural products. 相似文献
16.
Nícolas de Castro Campos Pinto Elita Scio 《Plant foods for human nutrition (Dordrecht, Netherlands)》2014,69(3):189-195
The exploration of nature as a source of sustainable, novel bioactive substances continues to grow as natural products play a significant role in the search for new therapeutic and agricultural agents. In this context, plants of the genus Pereskia (Cactaceae) have been studied for their biological activities, and are evolving as an interesting subject in the search for new, bioactive compounds. These species are commonly used as human foodstuffs and in traditional medicine to treat a variety of diseases. This review focuses on the bioactivity and chemical composition of the genus Pereskia, and aims to stimulate further studies on the chemistry and biological potential of the genus. 相似文献
17.
Mariano Catanesi Giulia Caioni Vanessa Castelli Elisabetta Benedetti Michele dAngelo Annamaria Cimini 《Marine drugs》2021,19(1)
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. 相似文献
18.
19.
Qi-Ting Zhang Ze-Dong Liu Ze Wang Tao Wang Nan Wang Ning Wang Bin Zhang Yu-Fen Zhao 《Marine drugs》2021,19(2)
Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. This paper highlights the anticancer linear and cyclic small peptides in marine resources and presents a review of peptides and the derivatives and their mechanisms. 相似文献
20.
Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared. 相似文献