Potential Of Marine Natural Products Research Articles

Exploring the potential of marine natural products in drug development: A comprehensive review

The discovery of drugs from marine natural products has witnessed a significant resurgence in recent years. A diverse range of marine organisms, including cone snails, bacteria, cyanobacteria, fungi, and halophytes, have yielded valuable compounds for drug development. These organisms contribute over 90% of the oceanic biomass, offering unique chemical properties with great potential, particularly in the field of anticancer research. The review highlights the historical successes in marine natural product-based drug discovery, emphasizing their novel chemical structures and bioactive properties. It sheds light on critical factors contributing to these discoveries, such as interdisciplinary collaborations between marine biologists, chemists, and pharmacologists, advanced isolation and characterization techniques, and the understanding of marine ecological niches. Challenges include limited supply, environmental concerns, and the complexity of chemical synthesis. Translating marine-derived compounds into viable pharmaceuticals requires rigorous testing, preclinical studies, and clinical trials. Looking forward, advances in research and technology, such as metagenomics and synthetic biology, offer promising avenues for faster and more efficient discovery and development of marine-derived drugs. The potential for uncovering new therapeutic agents remains vast, and the continued exploration of marine natural products holds the promise of significant breakthroughs in drug development while considering sustainable practices and environmental concerns.

Penicopeptide A (PPA) from the deep-sea-derived fungus promotes osteoblast-mediated bone formation and alleviates ovariectomy-induced bone loss by activating the AKT/GSK-3β/β-catenin signaling pathway

The potential of marine natural products as effective drugs for osteoporosis treatment is an understudied area. In this study, we investigated the ability of lead compounds from deep-sea-derived Penicillium solitum MCCC 3A00215 to promote bone formation in vitro and in vivo. We found that penicopeptide A (PPA) promoted osteoblast mineralization among bone marrow mesenchymal stem cells (BMSCs) in a concentration-dependent manner, and thus, we selected this natural peptide for further testing. Our further experiments showed that PPA significantly promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation and not affecting their chondrogenic differentiation. Mechanistic studies showed that PPA binds directly to the AKT and GSK-3β and activates phosphorylation of AKT and GSK-3β, resulting in the accumulation of β-catenin. We also evaluated the therapeutic potential of PPA in a female mouse model of ovariectomy-induced systemic bone loss. In this model, PPA treatment prevented decreases in bone volume and trabecular thickness. In conclusion, our in vitro and in vivo results demonstrated that PPA could promote osteoblast-related bone formation via the AKT, GSK-3β, and β-catenin signaling pathways, indicating the clinical potential of PPA as a candidate compound for osteoporosis prevention.

The landscape of nature-derived antimalarials-potential of marine natural products in countering the evolving Plasmodium

Malaria poses several challenges to the global research community on both diagnostic and therapeutic fronts. Most prominent of them are deletion of target genes (pfhrp2/3) used in rapid diagnostic tests (RDTs) and the emergence of resistance against frontline antimalarials by the evolving parasite. Exploration of novel therapeutics for malaria in view of limited vaccine options is a promising resort for malaria control and elimination. The scope of marine-derived chemotherapeutics is exciting, with a significant number of FDA-approved drugs or therapeutic leads under clinical trials for other diseases. This review article discusses the significant antimalarial potential of marine-derived natural products extracted from diverse biota including sponges, bacteria, sea hare and algae etc. Bioassay-guided fractionation of raw extracts from marine organisms for lead identification and further structural characterization of purified compounds compose a sustainable marine-derived drug discovery pipeline; which can be particularly diverted towards the exploration of antimalarials. It is to be noted that the Indian peninsula is largely unexplored, particularly for antimalarials screening; which has a huge marine biodiversity owing to the three distinct water bodies- Bay of Bengal, Indian Ocean and Arabian sea. This review also envisions a collaborative initiative to explore the potential of marine natural products in an economically feasible manner.

Anticancer Potential of Green Synthesized Silver Nanoparticles of the Soft Coral Cladiella pachyclados Supported by Network Pharmacology and In Silico Analyses.

Cladiella-derived natural products have shown promising anticancer properties against many human cancer cell lines. In the present investigation, we found that an ethyl acetate extract of Cladiella pachyclados (CE) collected from the Red Sea could inhibit the human breast cancer (BC) cells (MCF and MDA-MB-231) in vitro (IC50 24.32 ± 1.1 and 9.55 ± 0.19 µg/mL, respectively). The subsequent incorporation of the Cladiella extract into the green synthesis of silver nanoparticles (AgNPs) resulted in significantly more activity against both cancer cell lines (IC50 5.62 ± 0.89 and 1.72 ± 0.36, respectively); the efficacy was comparable to that of doxorubicin with much-enhanced selectivity. To explore the mode of action of this extract, various in silico and network-pharmacology-based analyses were performed in the light of the LC-HRESIMS-identified compounds in the CE extract. Firstly, using two independent machine-learning-based prediction software platforms, most of the identified compounds in CE were predicted to inhibit both MCF7 and MDA-MB-231. Moreover, they were predicted to have low toxicity towards normal cell lines. Secondly, approximately 242 BC-related molecular targets were collected from various databases and used to construct a protein–protein interaction (PPI) network, which revealed the most important molecular targets and signaling pathways in the pathogenesis of BC. All the identified compounds in the extract were then subjected to inverse docking against all proteins hosted in the Protein Data bank (PDB) to discover the BC-related proteins that these compounds can target. Approximately, 10.74% of the collected BC-related proteins were potential targets for 70% of the compounds identified in CE. Further validation of the docking results using molecular dynamic simulations (MDS) and binding free energy calculations revealed that only 2.47% of the collected BC-related proteins could be targeted by 30% of the CE-derived compounds. According to docking and MDS experiments, protein-pathway and compound-protein interaction networks were constructed to determine the signaling pathways that the CE compounds could influence. This paper highlights the potential of marine natural products as effective anticancer agents and reports the discovery of novel anti-breast cancer AgNPs.

Biomedical applications and therapeutic potential of marine natural products and marine algae

Recently there is an increase in the interest in the secondary or non-primary metabolites produced by the marine flora and fauna. It has become the center of attraction of chemists and pharmacologists in the previous decades. Stakeholders of the natural viewpoint emphasize that the examination of new and unusual organic molecules from marine organisms while the synthetic stakeholders' faiths in targeting these novel structures for the development of new analogs and new synthetic strategies and methodologies. The chemistry of marine organisms has changed dramatically in concern of investigating rationale. Analogous to the examination of terrestrial plants, many of the recent research and studies have concentrated on the potential application of marine extracted products in the treatment, curing of human diseases, and various other works. Marine products are the major components having biomedical-oriented natural products which can be used for various purposes. Marine natural products have enough potential to work prominently and also assisting in various kinds of human needs and works. In this review, we will be focusing on prominently their works, role in biomedical-related aspects.

Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review.

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

Marine natural products targeting the eukaryotic cell membrane.

The cell membrane, with high fluidity and alternative curvatures, maintains the robust integrity to distinguish inner and outer space of cells or organelles. Lipids are the main components of the cell membrane, but their functions are largely unknown. Even the visualization of lipids is not straightforward since modification of lipids often hampers its correct physical properties. Many natural products target cell membranes, some of which are used as pharmaceuticals and/or research tools. They show specific recognition on lipids, and thus exhibit desired pharmacological effects and unique biological phenotypes. This review is a catalog of marine natural products that target eukaryotic cell membranes. Chemical structures, biological activities, and molecular mechanisms are summarized. I hope that this review will be helpful for readers to notice the potential of marine natural products in the exploration of the function of lipids and the druggability of eukaryotic cell membranes.

In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease

The target for COVID-19 has been successfully crystallized along with its inhibitor, named SARS-CoV-2 main protease, making it easier for drug discovery and development. Sponge (Clathria Sp.) is a marine species that can be found in Indonesia and has a unique chemical structure that is still rarely explored in its properties. Therefore, this study aims to examined the potential of marine natural products from sponge (Clathria Sp.) as SARS-CoV-2 main protease inhibitor using in silico method. The ligand structures were obtained from the Knapsack database and the protein structure obtained from the RCSB site with the PDB code: 6LU7. The molecular docking method was validated by re-docked the native ligand and calculated the RMSD value. The compounds contained in Sponge were docked into the active site of the protein based on the validated methods. Afterward, the molecular dynamics were performed for 100 ns simulation, then analyzed its system complex stability. The RMSD 1.329 Å was obtained by re-docked of native ligand which indicates that the docking method was valid. Molecular docking of the ligands showed mirabilin_G has binding energy −7.38 kcal/mol, compared to the native ligand N3 inhibitor that is −7.30 kcal/mol, and the ligand showed good stability from molecular dynamics simulation indicated by RMSD, RMSF and MM-PBSA binding free energy similar to the inhibitor during 100 ns simulation. Its indicated the potential of the compounds contained in the sponge as inhibitor of SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma

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.

In silico analysis of sea cucumber bioactive compounds as anti-breast cancer mechanism using autodock vina

In recent years, the potential of marine natural products as anticancer agents, specifically for breast cancer, has been examined. The sea cucumber (Holothuroidea: Echinodermata) is known to contain triterpene glycosides, which have shown anticancer or cytotoxic activity. In this research, molecular docking of selected sea cucumber bioactive compounds was conducted on five receptor targets that play an important role in breast cancer: estrogen receptor alpha (ER-α), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), progesterone receptor (PR), and insulin-like growth factor 1 receptor (IGFR1). The purpose of this was to observe the interaction between active compounds and the active site of breast cancer receptor targets. Holothurin A gave the lowest binding energy (-7.1 kcal/mol) and was involved in a hydrogen bond with amino acid His-516 when superposition towards to E4D cocrystal was present. Holothurin A also had a similar posing with raloxifene, in which the hydrogen bond with His-516 with a RMSD value of 3.3 A was observed with superposition towards to the positive control raloxifene. The analysis and visualization results of 24-dehidroechinoside that was superposed on E4D cocrystal, BMI cocrystal, and positive control raloxifene showed that 24-dehidroechinoside had a hydrophobic interaction with amino-acid residue Leu-346, a strong hydrogen bond to Gln-977, as well as a hydrogen bond to Thr-347 in a distance of 3.7 A, and a hydrophobic interaction with amino-acid residue Ala-350. The most potent in silico anti-breast cancer compounds in sea cucumbers are holothurin A and 24-dehidroechinoside. Holothurin A is active as an anti-breast cancer agent by inhibiting ER-α, while 24-dehidroechinoside inhibits both ER-α and IGFR1.

Zebrafish-Based Discovery of Antiseizure Compounds from the North Sea: Isoquinoline Alkaloids TMC-120A and TMC-120B.

There is a high need for the development of new and improved antiseizure drugs (ASDs) to treat epilepsy. Despite the potential of marine natural products (MNPs), the EU marine biodiscovery consortium PharmaSea has made the only effort to date to perform ASD discovery based on large-scale screening of MNPs. To this end, the embryonic zebrafish photomotor response assay and the larval zebrafish pentylenetetrazole (PTZ) model were used to screen MNP extracts for neuroactivity and antiseizure activity, respectively. Here we report the identification of the two known isoquinoline alkaloids TMC-120A and TMC-120B as novel antiseizure compounds, which were isolated by bioactivity-guided purification from the marine-derived fungus Aspergillus insuetus. TMC-120A and TMC-120B were observed to significantly lower PTZ-induced seizures and epileptiform brain activity in the larval zebrafish PTZ seizure model. In addition, their structural analogues TMC-120C, penicisochroman G, and ustusorane B were isolated and also significantly lowered PTZ-induced seizures. Finally, TMC-120A and TMC-120B were investigated in a mouse model of drug-resistant focal seizures. Compound treatment significantly shortened the seizure duration, thereby confirming their antiseizure activity. These data underscore the possibility to translate findings in zebrafish to mice in the field of epilepsy and the potential of the marine environment for ASD discovery.

Antitumor Potential of Marine Natural Products: A Mechanistic Investigation.

Compounds obtained from natural resources have become important candidates in the discovery and development of drugs. Over the past few decades, marine resources have gradually attracted a large amount of attention from researchers, and many compounds with varying structures and activities have been derived from various marine resources. Since the ocean experiences more variable temperatures, lower oxygen levels and less light than the terrestrial environment, marine resources offer a substantial number of organisms that are not available or rarely detected on land. Researchers expect that they can discover agents from marine organisms that exhibit good activity for diseases. Of the marine compounds acquired, the majority have shown to have good antitumor activity, and range in phases from clinical trials up to being used in the clinic. These natural products operate through different pathways and have unique antitumor effects that include inducing cell apoptosis, inhibiting cell proliferation and influencing cell migration. A variety of drugs have been used for cancer treatment during the last few years, but it has not been possible to greatly extend the survival time of advanced cancer patients. In addition, researchers are actively looking for compounds to overcome problems that include a lack of effective drugs to control the transfer of cancer cells and the development of drug-resistant microbes. Here, we summarize the marine natural products that have been obtained over the past few years, and analyze their antitumor effects and mechanisms. Our research will provide a significant basis for anticancer drug screening and development.

From Marine Venoms to Drugs: Efficiently Supported by a Combination of Transcriptomics and Proteomics.

The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the rapid development of next-generation sequencing (NGS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), it has been much easier and faster to identify more toxins and predict their functions with bioinformatics pipelines, which pave the way for novel drug developments. Here we provide an overview of related bioinformatics pipelines that have been supported by a combination of transcriptomics and proteomics for identification and function prediction of novel marine toxins.

Polysaccharides from the Marine Environment with Pharmacological, Cosmeceutical and Nutraceutical Potential.

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides represent some of the most abundant bioactive substances in marine organisms. In fact, many marine macro- and microorganisms are good resources of carbohydrates with diverse applications due to their biofunctional properties. By acting on cell proliferation and cycle, and by modulating different metabolic pathways, marine polysaccharides (including mainly chitin, chitosan, fucoidan, carrageenan and alginate) also have numerous pharmaceutical activities, such as antioxidative, antibacterial, antiviral, immuno-stimulatory, anticoagulant and anticancer effects. Moreover, these polysaccharides have many general beneficial effects for human health, and have therefore been developed into potential cosmeceuticals and nutraceuticals. In this review we describe current advances in the development of marine polysaccharides for nutraceutical, cosmeceutical and pharmacological applications. Research in this field is opening new doors for harnessing the potential of marine natural products.

The marine biodiscovery pipeline and ocean medicines of tomorrow

Marine organisms possess the capacity to produce a variety of unique and biologically potent natural products for treating human diseases, many of which are currently commercially available or are in advanced clinical trials. Here we provide a short review on progress in the field and discuss a case study of an EU-funded project, PharmaSea, which aims to discover novel products for the treatment of infections, inflammation and neurodegenerative diseases. Research in this sector is opening new doors for harnessing the potential of marine natural products with pharmaceutical properties.

Safety of Malaysian marine endophytic fungal extract S2 from a brown seaweed Turbinaria conoides

Objective: To evaluate the in vivo acute toxicity and antioxidant activity of the marine endophytic fungus extract S2 isolated from Turbinaria conoides. Methods: Two doses (100 mg/kg and 400 mg/kg) of the S2 extract were administered to rats orally for acute toxicity and antioxidant test. The body weight, relative weight of six organs, haematological, biochemical and antioxidant properties were investigated on Day 14. Results: A single oral dose treatment did not cause any mortality or observable adverse effects in rats. No significant variations in the body and organ weights between the control and the treated groups were observed. Heamatological analysis and clinical blood chemistry also did not reveal any toxic effects of the extract. The total white blood cell count and haemoglobin levels were increased. The levels of total serum cholesterol in males treated with 100 and 400 mg/kg were significantly (P<0.05) decreased (1.28 and 1.34 mmol/L respectively) compared to control (1.55 mmol/L) rats. Pathologically, neither gross abnormalities nor histopathological changes were observed. This study showed strong evidence of the non-toxic effects of S2 extract. Furthermore the extract exhibited significant (P<0.05) antioxidant activity through increased levels of superoxide dismutase and glutathione peroxidase enzymes in serum, liver and kidney. Conclusions: The research findings from the present study showed the potential of marine natural products particularly in Malaysia as a source of bioactive compounds. Marine endophytic fungi as a potential source of anticancer drugs with great potential as they are potent yet safe, thus deserving further extensive investigation.

Optimization, pharmacophore modeling and 3D-QSAR studies of sipholanes as breast cancer migration and proliferation inhibitors

Sipholenol A, a triterpene isolated from the Red Sea sponge Callyspongia siphonella, was previously shown to reverse multidrug resistance in P-glycoprotein-overexpressing cancer cells. Moreover, sipholanes showed promising in vitro inhibitory effects against the invasion and migration of the metastatic human breast cancer cell line MDA-MB-231. The breast tumor kinase (Brk), a mediator of cancer cell phenotypes important for proliferation, survival, and migration, was proposed as a potential target. This study reports additional semisynthetic optimization of sipholenol A esters to improve the breast cancer antimigratory and antiproliferative activities as well as Brk phosphorylation inhibition. Fifteen new sipholenol A analogs (25–39) were semisynthesized. Sipholenol A 4β-4′,5′-dichlorobenzoate ester (29) was the most potent, with an IC50 value of 1.3 μM in the migration assay. The level of Brk phosphorylation inhibition of 29 was assessed using the Z′-LYTE™ kinase assay and Western blot analysis. Active analogs showed no toxicity on the non-tumorigenic epithelial breast cell line MCF10A at doses equal to their IC50 values or higher in migration and proliferation assays, suggesting their selectivity towards malignant cells. Pharmacophore modeling and 3D-QSAR studies were conducted to identify important pharmacophoric features and correlate 3D-chemical structure with activity. These studies provided the evidence for future design of novel antimigratory compounds based on a simplified sipholane structure possessing rings A and B (perhydrobenzoxepine) connected to substituted aromatic esters, with the elimination of rings C and D ([5,3,0]bicyclodecane system). This will enable the future synthesis of the new active entities feasibly and cost-effectively. These results demonstrate the potential of marine natural products for the discovery of novel scaffolds for the control and management of metastatic breast cancer.

Bioactive natural products from Chinese marine flora and fauna.

In recent decades, the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists. Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges, soft corals, and mollusks), resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins. Of particular interest is the fact that many of these compounds show promising biological activities, including cytotoxic, antibacterial, and enzyme inhibitory effects. By describing representative studies, this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade. Several interesting examples are discussed in detail.

Biotechnological potential of marine natural products

The number of marine natural products (MNPs) that have been applied to biotechnological industry is very limited, although nearly 20 000 new compounds were discovered from marine organisms since the birth of MNPs in the early 1970s. However, it is apparent that they have a significant potential as pharmaceuticals, cosmetics, nutraceuticals, research tools, and others. This article focuses on selective antitumor metabolites isolated from marine sponges and tunicates and their modes of action, as well as promising candidates for nontoxic antifoulants discovered from marine organisms.

Antidepressant Secondary Metabolites from Three Florida Sponges

Depression is very common nervous system disorder and according to WHO it is the third most common illness in the world after infectious diseases and heart diseases [1]. All clinically used antidepressant drugs suffer from very serious side effect (e.g. suicidal thoughts) and require about six weeks before the full therapeutic effect occurs [2]. In our search for possible leads to control depression we have investigated three Florida sponges: Verongula rigida, Smenospongia aurea and S. cerebriformis. Several known compounds were isolated and evaluated in the porsolt forced swim test and chick anxiety-depression model. Among the examined metabolites, 5,6-dibromo-N,N-dimethyltryptamine (1) exhibited significant antidepressant action while 5-bromo-N,N-dimethyltryptamine (2) caused reduction in locomotor activity, which indicates potential sedative action. This study reveals the potential of marine natural products as leads to control depression. Acknowledgements: We are grateful to Mr. J. Diers for testing (1) in the forced swim test. This research was conducted pursuant to the Florida Fish and Wildlife Conservation Division of Marine Fisheries Management Special Activity License.