Marine Compounds Research Articles

Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial-mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development. Despite advancements in CDK5-targeted inhibitor research, the range of compounds available for clinical and preclinical trials remains limited. The marine environment has emerged as a prolific source of diverse natural products with noteworthy biological activities, including anti-cancer properties. In this study, we screened a library of 47,450 marine natural compounds from the comprehensive marine natural product database (CMNPD) to assess their binding affinity with CDK5. Marine compounds demonstrating superior binding affinity compared to a reference compound were identified through high-throughput virtual screening, standard precision and extra-precision Glide docking modes. Refinement of the selected molecules involved evaluating molecular mechanics-generalized born surface area (MM/GBSA) free binding energy. The three most promising compounds, (excoecariphenol B, excoecariphenol A, and zyzzyanone B), along with the reference, exhibiting favorable binding characteristics were chosen for molecular dynamics (MD) simulations for 200 nanoseconds. These compounds demonstrated interaction stability with the target during MD simulations. The marine compounds identified in this study hold potential as effective CDK5 inhibitors and warrant subsequent experimental validation.

Alzheimer's disease from a diabetic brain: Exploring the molecular process to determine the potential therapy target from marine sources

Background: The prevalence of Alzheimer’s Disease (AD) among Type 2 Diabetes Mellitus (T2D) patients has reached almost 30%. Despite the rapid development, treatments for patients with T2D have not succeeded in controlling the neurodegenerative processes that occur in these patients' brains, leading to AD pathology. Several studies have demonstrated that marine sources can inhibit several AD pathogenesis pathways in T2D patients. This review aimed to determine the effect of marine species-sourced compounds at the molecular level in inhibiting and preventing the pathogenesis of AD in T2D patients. Method: Combinations of several terms were used to search for peer-reviewed literature published in PubMed, Scopus, and Google Scholar. Result: Marine organisms-sourced compounds inhibited various target signalling pathways between T2D and AD, such as an inhibitor of β-site-amyloid precursor protein cleaving enzyme 1 (BACE1) also known as β-secretase, glycogen synthase kinase-3 beta (GSK3B), insulin degradation enzyme (IDE), the mammalian target of rapamycin (mTOR), nuclear factor kappa-light-chain-enhancer (NF-κb), and nuclear factor erythroid 2-related factor 2 (Nrf2). Conclusion: Marine sources can be considered as a potential therapy to prevent or slow AD progression in T2D patients.

Unveiling the potential of marine compounds as quorum sensing inhibitors targeting Pseudomonas aeruginosa's LasI: A computational study using molecular docking and molecular dynamics.

Antimicrobial resistance (AMR) poses a significant threat to global public health, with multidrug-resistant Pseudomonas aeruginosa being a leading cause of mortality, accounting for 18%-61% of deaths annually. The quorum sensing (QS) systems of P. aeruginosa, particularly the LasI-LasR system, play a crucial role in promoting biofilm formation and expression of virulent genes, which contribute to the development of AMR. This study focuses on LasI, the mediator of biofilm formation for identifying its inhibitors from a marine compound database comprising of 32 000 compounds using molecular docking and molecular simulation techniques. The virtual screening and docking experiments demonstrated that the top 10 compounds exhibited favorable docking scores of <-7.19 kcal/mol compared to the reported inhibitor 3,5,7-Trihydroxyflavone with a docking score of -3.098 kcal/mol. Additionally, molecular mechanics/Poisson-Boltzmann generalized born surface area (MM-GBSA) analyses were conducted to assess these compounds' suitability for further investigation. Out of 10 compounds, five compounds demonstrated high MM-GBSA binding energy (<-35.33 kcal/mol) and were taken up for molecular dynamics simulations to evaluate the stability of the protein-ligand complex over a 100 ns period. Based on root mean square deviation, root mean square fluctuation, radius of gyration, and hydrogen bond interactions analysis, three marine compounds, namely MC-2 (CMNPD13419) and MC-3 (CMNPD1068), exhibited consistent stability throughout the simulation. Therefore, these compounds show potential as promising LasI inhibitors and warrant further validation through in vitro and in vivo experiments. By exploring the inhibitory effects of these marine compounds on P. aeruginosa's QS system, this research aims to contribute to the development of novel strategies to combat AMR.

Natural Marine Anticancer compounds and their derivatives used in Clinical Trials

Cancer remains a global challenge for clinicians and researchers alike, with an increasing mortality rate. Despite enormous progress in anticancer drug discovery, there is a constant demand for novel therapeutic agents due to resistance to existing chemotherapeutic drugs and their adverse side effects. Natural anticancer drugs have been shown to be both effective and safe in the treatment of cancer. Over 70% of the earth's surface and 95% of its tropical biosphere are covered by the oceans. 50% of the Earth's biodiversity, or 34 out of the 36 phyla, is made up of marine organisms. The majority of oceanic organisms are members of the marine flora, which also includes sponges, seaweed, algae, cyanobacteria, and marine fungi. These marine sources have created a significant opportunity for the discovery of novel anticancer compounds due to their taxonomically diverse and biological characteristics. Numerous marine compounds with potent anticancer properties have recently been identified, and clinical studies have demonstrated their effectiveness. The majority of them are sulfated polysaccharides and polyphenols, which are renowned for their powerful antioxidant, antitumor. Thus, the current chapter focuses on natural anticancer compounds and their derivatives that are undergoing clinical trials.

Ircinia ramosa Sponge Extract (iSP) Induces Apoptosis in Human Melanoma Cells and Inhibits Melanoma Cell Migration and Invasiveness.

Marine compounds represent a varied source of new drugs with potential anticancer effects. Among these, sponges, including those belonging to the Irciniidae family, have been demonstrated to exert cytotoxic effects on different human cancer cells. Here, we investigated, for the first time, the therapeutic effect of an extract (referred as iSP) from the sponge, Ircinia ramosa (Porifera, Dictyoceratida, and Irciniidae), on A375 human melanoma cells. We found that iSP impaired A375 melanoma cells proliferation, induced cell death through caspase-dependent apoptosis and arrested cells in the G1 phase of the cell cycle, as demonstrated via both flow cytometry and qPCR analysis. The proapoptotic effect of iSP is associated with increased ROS production and mitochondrial modulation, as observed by using DCF-DHA and mitochondrial probes. In addition, we performed wound healing, invasion and clonogenic assays and found that iSP was able to restrain A375 migration, invasion and clonogenicity. Importantly, we observed that an iSP treatment modulated the expression of the EMT-associated epithelial markers, E-CAD and N-CAD, unveiling the mechanism underlying the effect of iSP in modulating A375 migration and invasion. Collectively, this study provides the first evidence to support the role of Ircinia ramosa sponge extracts as a potential therapeutic resource for the treatment of human melanoma.

A Review Assessment of Fiber-Reinforced Polymers for Maritime Applications

Composite materials, comprised of fibre-reinforced polymers, offer a high strength-to-weight ratio, making them excellent for the building of complex, lightweight structures in several industries, including the marine industry. There is an improvement in fuel efficiency and cost-effectiveness in general marine component developments as a result of the lightweight and flexible design characteristics. Fibre-reinforced polymer (FRP) composites are often used to construct boats, ships, and other marine compounds, such as the hull, column beams, piling structures, and other internal ship components, since they meet the aforementioned characteristics. In terms of durability, rigidity, and corrosion resistance, these FRPs may readily replace their conventional metal counterparts. So, thisreview gives an overview of FRP composites' application in marine industries for various potential applications. Fibre-reinforced polymer composites offer a significant advantage in strength and weight when compared to conventional materials.

Potential Use of Marine Compounds to Modulate the Ubiquitin-Proteasome System

Potential Use of Marine Compounds to Modulate the Ubiquitin-Proteasome System

Dietary marine-derived ingredients for stimulating hair cell cycle

In normal condition human hair growth occurs through three phases, anagen (growth phase included about 85 % of hairs, last from 2 to 6 years), catagen (transitional phase lasting up to 2 weeks) and telogen (resting phase which last from 1 to 4 months). Natural dynamics of the hair growth process can be impaired by several factors, such as genetic predisposition, hormonal disorders, aging, poor nutrition or stress, which can lead to the slowdown in the growth of hair or even hair loss. The aim of the study was to assess the hair growth promotion effect of marine-derived ingredients, hair supplement Viviscal® and its raw components (marine protein complex AminoMarC®, shark and oyster extract). Cytotoxicity, production of alkaline phosphatase and glycosaminoglycans, as well as expression of genes involved in hair cycle-related pathways were investigated using dermal papilla cells, both immortalized and primary cell lines. Tested marine compounds showed no evidence of cytotoxicity under in vitro conditions. Viviscal® significantly increased proliferation of dermal papilla cells. Moreover, tested samples stimulated cells to produce alkaline phosphatase and glycosaminoglycans. Increased expression of hair cell cycle-related genes was also observed. The obtained results indicate that marine-derived ingredients stimulate hair growth through anagen activation.

Marine Algal Polyphenols as Skin Protective Agents: Current Status and Future Prospectives.

The skin is the outermost anatomical barrier, which plays a vital role in the maintenance of internal homeostasis and protection against physical, chemical, and biological detractors. Direct contact with various stimuli leads to several physiological changes that are ultimately important for the growth of the cosmetic industry. Due to the consequences of using synthetic compounds in skincare and cosmeceutical-related industries, the pharmaceutical and scientific communities have recently shifted their focus to natural ingredients. The nutrient-rich value of algae, which are some of the most interesting organisms in marine ecosystems, has attracted attention. Secondary metabolites isolated from seaweeds are potential candidates for a wide range of economic applications, including food, pharmaceuticals, and cosmetics. An increasing number of studies have focused on polyphenol compounds owing to their promising biological activities against oxidation, inflammation, allergies, cancers, melanogenesis, aging, and wrinkles. This review summarizes the potential evidence of the beneficial properties and future perspectives of using marine macroalgae-derived polyphenolic compounds for advancing the cosmetic industry.

Antioxidant and chemotherapeutic efficacies of seaweed-derived phlorotannins in cancer treatment: A review regarding novel anticancer drugs.

The ineffectiveness of traditional cancer therapies due to drug resistance, nontargeted delivery, and chemotherapy-associated adverse side effects has shifted attention to bioactive phytochemicals. Consequently, research efforts toward screening and identification of natural compounds with anticancer properties have increased in recent years. Marine seaweed-derived bioactive compounds, such as polyphenolic compounds, have exhibited anticancer properties. Phlorotannins (PTs), a major group of seaweed-derived polyphenolic compounds, have emerged as powerful chemopreventive and chemoprotective compounds, regulating apoptotic cell death pathways both in vitro and in vivo. In this context, this review focuses on the anticancer activity of polyphenols isolated from brown algae, with a special reference to PTs. Furthermore, we highlight the antioxidant effects of PTs and discuss how they can impact cell survival and tumor development and progression. Moreover, we discussed the potential therapeutic application of PTs as anticancer agents, having molecular mechanisms involving oxidative stress reduction. We have also discussed patents or patent applications that apply PTs as major components of antioxidant and antitumor products. With this review, researcher may gain new insights into the potential novel role of PTs, as well as uncover a novel cancer-prevention mechanism and improve human health.

Computational Characterization of Xyloketal B with Human C-Reactive Protein For Management of Kawasaki Disease (KD)

The most common underlying cause of acquired cardiovascular disease in developed countries is Kawasaki disease (KD), a systemic vasculitis. The most serious and common consequence of KD is the growth of coronary artery involvement, however therapy with intravenous gammaglobulin can minimized this issue. There are various limitations of using intravenous gammaglobulin which further make researchers to look for alternative medicine. It has been found that marine natural products and compounds from natural sources are having cardioprotective nature. The present research aims at filling the gap with computational analysis to explore the target ability y of Xyloketal B on human C-Reactive Protein having vital role in Kawasaki disease. It has been found that the marine compound has the ability to inhibit CRP with considerable negative biding energy of-8.47Kcal/mol. The present stdy may aid researchers to explore new invention having the potential for enzymatic and chemical modification of the molecule for the management of KD. Patients having a history of coronary artery disease, involvement are encouraged to have long-term follow-up.

Potential Active Marine Peptides as Anti-Aging Drugs or Drug Candidates

Aging is an irreversible physiological process in the human body, and the aging characteristics of the body that accompany this process also lead to many other chronic diseases, such as neurodegenerative diseases represented by Alzheimer's disease and Parkinson's disease, cardiovascular diseases, hypertension, obesity, cancer, and so on. The marine environment is highly biodiverse, the natural active products of these organisms constitute a vast treasure trove of marine drugs or drug candidates that play an essential role in disease prevention and treatment, and the active peptide products among them have received special attention because of their unique chemical properties. Therefore, the development of marine peptide compounds as anti-aging drugs is emerging as an important research area. This review highlights the currently available data on marine bioactive peptides with anti-aging potential from 2000 to 2022 by analyzing the prevalent aging mechanisms, critical aging metabolic pathways and well-established multi-omics aging characteristics, as well as grouping different bioactive and biological species lines of peptides from marine organisms and discussing their research modalities and functional characteristics. Active marine peptides is a promising topic to explore and to develop their potential as anti-aging drugs or drug candidates. We expect this review to be instructive for future marine drug development and to reveal new directions for future biopharmaceuticals.

Unifying the Synthesis of a Whole Family of Marine Meroterpenoids through a Biosynthetically Inspired Sequence of 1,2-Hydride and Methyl Shifts as Key Step

Marine meroterpenoids have attracted a great deal of attention from synthetic research groups due to their attractive and varied biological activities and their unique and diverse structures. In most cases, however, further biological studies have been severely limited mainly to the scarcity of natural supply and because almost none of the reported syntheses methods has enabled unified access for a large number of marine meroterpenoids with aureane and avarane skeletons. Based on our previous publications and the study of recent manuscripts on marine meroterpenoids, we have conceived a unified strategy for these fascinating marine compounds with aureane or avarane skeletons using available drimane compounds as starting materials. The key step is a biosynthetic sequence of 1,2-hydride and methyl shifts. This strategy is of great synthetic value to access marine meroterpenoids through easy chemical synthetic procedures. Finally, several retrosynthetic proposals are made for the future synthesis of several members of this class of meroterpenoids, focused on consolidating these 1,2-rearrangements as a versatile and unified strategy that could be widely used in the preparation of these marine meroterpenoids.

Promising Antiparasitic Natural and Synthetic Products from Marine Invertebrates and Microorganisms.

Parasitic diseases still threaten human health. At present, a number of parasites have developed drug resistance, and it is urgent to find new and effective antiparasitic drugs. As a rich source of biological compounds, marine natural products have been increasingly screened as candidates for developing new antiparasitic drugs. The literature related to the study of the antigenic animal activity of marine natural compounds from invertebrates and microorganisms was selected to summarize the research progress of marine compounds and the structure-activity relationship of these compounds in the past five years and to explore the possible sources of potential antiparasitic drugs for parasite treatment.

Marine-Derived Natural Product HDYL-GQQ-495 Targets P62 to Inhibit Autophagy.

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFPKI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFPKI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis.

Antifungal and Antibacterial Activities of Isolated Marine Compounds.

To combat the ineffectiveness of currently available pharmaceutical medications, caused by the emergence of increasingly resistant bacterial and fungal strains, novel antibacterial and antifungal medications are urgently needed. Novel natural compounds with antimicrobial activities can be obtained by exploring underexplored habitats such as the world's oceans. The oceans represent the largest ecosystem on earth, with a high diversity of organisms. Oceans have received some attention in the past few years, and promising compounds with antimicrobial activities were isolated from marine organisms such as bacteria, fungi, algae, sea cucumbers, sea sponges, etc. This review covers 56 antifungal and 40 antibacterial compounds from marine organisms. These compounds are categorized according to their chemical structure groups, including polyketides, alkaloids, ribosomal peptides, and terpenes, and their organismal origin. The review provides the minimum inhibitory concentration MIC values and the bacterial/fungal strains against which these chemical compounds show activity. This study shows strong potential for witnessing the development of new novel antimicrobial drugs from these natural compounds isolated and evaluated for their antimicrobial activities.

Combination of marine bioactive compounds and extracts for the prevention and treatment of chronic diseases.

In recent years, marine-based functional foods and combination therapy are receiving greater recognition for their roles in healthy lifestyle applications and are being investigated as viable and effective strategies for disease treatment or prevention. This review article presents and discusses the relevant scientific publications that have studied the synergistic and additive effects of natural marine bioactive compounds and extract combinations with anti-obesity, anti-inflammatory, antioxidant, and chemopreventive activities in the last two decades. The paper presents the mechanism of action and health benefits of developed combinations and discusses the limitation of the studies. Furthermore, it recommends alternatives and directions for future studies. Finally, it highlights the factors for developing novel combinations of marine bioactive compounds. Combination of marine bioactive compounds or extracts affords synergistic or additive effects by multiple means, such as multi-target effects, enhancing the bioavailability, boosting the bioactivity, and neutralizing adverse effects of compounds in the mixture. For the development of marine-based combinations, there are key points for consideration and issues to address: knowledge of the mechanism of action of individual compounds and their combinations, optimum ratio and dosing of compounds, and experimental models must all be taken into account. Strategies to increase the number and diversity of marine combinations, and further development of marine-based functional foods, are available. However, only a small number of natural marine bioactive combinations have been assessed, and most research has been focused on fish oil and carotenoid synergy. Therefore, more research and resources should be spent on developing novel marine bioactive combinations as functional foods and nutraceuticals.

Marine bioactive compounds as antibiofilm agent: a metabolomic approach.

The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.

Algae: Prospective and Futuristic Component for Cosmeceuticals

Skin is the most fundamental organ in the human body because it protects the body from the outside environment. There are several elements that can alter skin functioning and create a variety of disorders ranging from hyperpigmentation to skin cancer. A wide range of marine compounds, including both forms of micro- and macroalgae and fishing byproducts, are currently available in the cosmetic and cosmeceutical market. Several synthetic medications are promoted as providing skin protection, but they have various adverse effects. Algae is a natural phototropic plant that can endure any condition and has a variety of skin protective properties due to the presence of bioactive substances such as mycosporine-like amino acids, carotenoids, sulfated polysaccharides, sterols, polyphenols, and vitamins. It includes photoprotective chemicals such as UV absorbers, antioxidants, matrix-metalloproteinase inhibitors, anti-aging, and immunomodulatory properties. As a result, using algae as a cosmeceutical product can help to avoid a variety of skin diseases.

Organic matter variations in the deep marginal basin of the Western Tethys and links to various environments in isotopic Albian–Cenomanian Boundary Interval

In the latest Albian–lowermost Cenomanian, the palaeoenvironments along the northern margin in the Carpathian domain of the Western Tethys were characterized by deep basins with floors below the calcium compensation depth, which were filled with flysch and hemipelagic sediments. On the other hand, the terrestrial areas surrounding the Western Tethys to the north were covered by a diverse flora of gymnosperms and experienced an increase in the diversity of angiosperms; the latter was characterized by a rapid spread in most terrestrial environments. The flysch/hemipelagic succession of the Silesian Basin (the Polish part of the Outer Carpathians) contains a sedimentological record of organic-rich accumulation that is related to the carbon isotope excursion, known as the Albian–Cenomanian Boundary Interval (ACBI); its older part corresponds to Oceanic Anoxic Event 1d (OAE1d). Organic matter (OM) records from these noncalcareous sediments are characterized by the occurrence of both terrigenous and marine organic compounds, and an increase in their accumulation intensity occurred during OAE1d, similar to other Western Tethyan areas and their northern surroundings. Quantitative analyses of the OM compounds using petrographic and chemical methods indicate that the majority were redeposited from land and estuarine environments; however, the OAE1d strata (Alternans Level) and the lower part of the post-OAE1d black shale succession are also enriched in OM of marine origin. This enrichment is interpreted as the result of enhanced surface water productivity, most likely related to redistribution of nutrients from coastal areas during the sea level rise of the KAl8 eustatic cycle. OAE1d was also the period in which the degradation of OM took place under reducing conditions in the bottom waters (although they were not anoxic), which was possibly caused by poor ventilation. A high proportion of terrigenous/estuarine OM compounds redeposited in the Silesian Basin is characteristic, especially for the post-ACBI black and dark grey shales. A large amount of this OM type has undergone relatively rapid degradation as it has settled from the shallows through a well‑oxygenated water column in the epi-, meso- and bathypelagic zones. Some terrigenous OM came from forest fires that occurred in the catchment area and supplied material to the Silesian Basin.