Chemical Constituents and Anticancer Activities of Marine-Derived Fungus Trichoderma lixii.

The fungal genus Trichoderma is a rich source of structurally diverse secondary metabolites with remarkable pharmaceutical properties. The chemical constituents and anticancer activities of the marine-derived fungus Trichoderma lixii have never been investigated. In this study, a bioactivity-guided investigation led to the isolation of eleven compounds, including trichodermamide A (1), trichodermamide B (2), aspergillazine A (3), DC1149B (4), ergosterol peroxide (5), cerebrosides D/C (6/7), 5-hydroxy-2,3-dimethyl-7-methoxychromone (8), nafuredin A (9), and harzianumols E/F (10/11). Their structures were identified by using various spectroscopic techniques and compared to those in the literature. Notably, compounds 2 and 5-11 were reported for the first time from this species. Evaluation of the anticancer activities of all isolated compounds was carried out. Compounds 2, 4, and 9 were the most active antiproliferative compounds against three cancer cell lines (human myeloma KMS-11, colorectal HT-29, and pancreas PANC-1). Intriguingly, compound 4 exhibited anti-austerity activity with an IC50 of 22.43 µM against PANC-1 cancer cells under glucose starvation conditions, while compound 2 did not.

A High-Throughput Screening of a Natural Products Library for Mitochondria Modulators.

Mitochondria, the energy hubs of the cell, are progressively becoming attractive targets in the search for potent therapeutics against neurodegenerative diseases. The pivotal role of mitochondrial dysfunction in the pathogenesis of various diseases, including Parkinson's disease (PD), underscores the urgency of discovering novel therapeutic strategies. Given the limitations associated with available treatments for mitochondrial dysfunction-associated diseases, the search for new potent alternatives has become imperative. In this report, we embarked on an extensive screening of 4224 fractions from 384 Australian marine organisms and plant samples to identify natural products with protective effects on mitochondria. Our initial screening using PD patient-sourced olfactory neurosphere-derived (hONS) cells with rotenone as a mitochondria stressor resulted in 108 promising fractions from 11 different biota. To further assess the potency and efficacy of these hits, the 11 biotas were subjected to a subsequent round of screening on human neuroblastoma (SH-SY5Y) cells, using 6-hydroxydopamine to induce mitochondrial stress, complemented by a mitochondrial membrane potential assay. This rigorous process yielded 35 active fractions from eight biotas. Advanced analysis using an orbit trap mass spectrophotometer facilitated the identification of the molecular constituents of the most active fraction from each of the eight biotas. This meticulous approach led to the discovery of 57 unique compounds, among which 12 were previously recognized for their mitoprotective effects. Our findings highlight the vast potential of natural products derived from Australian marine organisms and plants in the quest for innovative treatments targeting mitochondrial dysfunction in neurodegenerative diseases.

The Ocean's Pharmacy: Health Discoveries in Marine Algae.

Non-communicable diseases (NCDs) represent a global health challenge, constituting a major cause of mortality and disease burden in the 21st century. Addressing the prevention and management of NCDs is crucial for improving global public health, emphasizing the need for comprehensive strategies, early interventions, and innovative therapeutic approaches to mitigate their far-reaching consequences. Marine organisms, mainly algae, produce diverse marine natural products with significant therapeutic potential. Harnessing the largely untapped potential of algae could revolutionize drug development and contribute to combating NCDs, marking a crucial step toward natural and targeted therapeutic approaches. This review examines bioactive extracts, compounds, and commercial products derived from macro- and microalgae, exploring their protective properties against oxidative stress, inflammation, cardiovascular, gastrointestinal, metabolic diseases, and cancer across in vitro, cell-based, in vivo, and clinical studies. Most research focuses on macroalgae, demonstrating antioxidant, anti-inflammatory, cardioprotective, gut health modulation, metabolic health promotion, and anti-cancer effects. Microalgae products also exhibit anti-inflammatory, cardioprotective, and anti-cancer properties. Although studies mainly investigated extracts and fractions, isolated compounds from algae have also been explored. Notably, polysaccharides, phlorotannins, carotenoids, and terpenes emerge as prominent compounds, collectively representing 42.4% of the investigated compounds.

Marine polysaccharides: Biological activities and applications in drug delivery systems.

The ocean is the common home of a large number of marine organisms, including plants, animals, and microorganisms. Researchers can extract thousands of important bioactive components from the oceans and use them extensively to treat and prevent diseases. In contrast, marine polysaccharide macromolecules such as alginate, carrageenan, Laminarin, fucoidan, chitosan, and hyaluronic acid have excellent physicochemical properties, good biocompatibility, and high bioactivity, which ensures their wide applications and strong therapeutic potentials in drug delivery. Drug delivery systems (DDS) based on marine polysaccharides and modified marine polysaccharide molecules have emerged as an innovative technology for controlling drug distribution on temporal, spatial, and dosage scales. They can detect and respond to external stimuli such as pH, temperature, and electric fields. These properties have led to their wide application in the design of novel drug delivery systems such as hydrogels, polymeric micelles, liposomes, microneedles, microspheres, etc. In addition, marine polysaccharide-based DDS not only have smart response properties but also can combine with the unique biological properties of the marine polysaccharide base to exert synergistic therapeutic effects. The biological activities of marine polysaccharides and the design of marine polysaccharide-based DDS are reviewed. Marine polysaccharide-based responsive DDS are expected to provide new strategies and solutions for disease treatment.

Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.

Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin entered clinical practice, but there is also a successfully marketed marine-derived bisindole compound called midostaurin that is used for the treatment of acute myeloid leukemia. In summary, investigations into the biological activity and clinical progress of marine-derived bisindoles have revealed their remarkable selectivity, minimal toxicity, and efficacy against various cancer cells. Consequently, they exhibit immense potential in the field of anti-tumor drug development, especially in the field of anti-tumor drug resistance. In the future, these compounds may serve as promising leads in the discovery and development of novel cancer therapeutics.

The therapeutic effects of marine sulfated polysaccharides on diabetic nephropathy.

Marine sulfated polysaccharide (MSP) is a natural high molecular polysaccharide containing sulfate groups, which widely exists in various marine organisms. The sources determine structural variabilities of MSPs which have high security and wide biological activities, such as anticoagulation, antitumor, antivirus, immune regulation, regulation of glucose and lipid metabolism, antioxidant, etc. Due to the structural similarities between MSP and endogenous heparan sulfate, a majority of studies have shown that MSP can be used to treat diabetic nephropathy (DN) in vivo and in vitro. In this paper, we reviewed the anti-DN activities, the dominant mechanisms and structure-activity relationship of MSPs in order to provide the overall scene of MSPs as a modality of treating DN.

The potential of marine-derived piperazine alkaloids: Sources, structures and bioactivities.

Marine-derived piperazine alkaloids (MDPAs) constitute a significant group of natural compounds known for their diverse structures and biological activities. Over the past five decades, substantial efforts have been devoted to isolating these alkaloids from marine sources and characterizing their chemical and bioactive profiles. To date, a total of 922 marine-derived piperazine alkaloids have been reported from various marine organisms. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and various other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of marine-derived piperazine alkaloids. This review also summarizes the structure-activity relationship (SAR) studies associated with the cytotoxicity of these compounds. In summary, our objective is to provide an overview of the research progress concerning marine-derived piperazine alkaloids, with the aim of fostering their continued development and utilization.

Embracing the era of antimicrobial peptides with marine organisms.

Covering: 2018 to Jun of 2023The efficiency of traditional antibiotics has been undermined by the proliferation of antibiotic-resistant pathogenic microorganisms, necessitating the pursuit of innovative therapeutic agents. Antimicrobial peptides (AMPs), which are part of host defence peptides found ubiquitously in nature, exhibiting a wide range of activity towards bacteria, fungi, and viruses, offer a highly promising candidate solution. The efficacy of AMPs can frequently be augmented via alterations to their amino acid sequences or structural adjustments. Given the vast reservoir of marine life forms and their distinctive ecosystems, marine AMPs stand as a burgeoning focal point in the quest for alternative peptide templates extracted from natural sources. Advances in identification and characterization techniques have accelerated the discoveries of marine AMPs, thereby stimulating AMP customization, optimization, and synthesis research endeavours. This review presents an overview of recent discoveries related to the intriguing qualities of marine AMPs. Emphasis will be placed upon post-translational modifications (PTMs) of marine AMPs and how they may impact functionality and potency. Additionally, this review considers ways in which marine PTM might support larger-scale, heterologous AMP manufacturing initiatives, providing insights into translational applications of these important biomolecules.

A review on marine source as anticancer agents.

This review investigates the potential of natural compounds obtained from marine sources for the treatment of cancer. The oceans are believed to contain physiologically active compounds, such as alkaloids, nucleosides, macrolides, and polyketides, which have shown promising effects in slowing human tumor cells both in vivo and in vitro. Various marine species, including algae, mollusks, actinomycetes, fungi, sponges, and soft corals, have been studied for their bioactive metabolites with diverse chemical structures. The review explores the therapeutic potential of various marine-derived substances and discusses their possible applications in cancer treatment.

Semisynthesis of Linariophyllenes A-C and Rumphellolide H, Structure Revisions and Proposed Biosynthesis Pathways.

The first semisynthetic routes toward terrestrial anti-inflammatory natural products linariophyllene A-C and the refined route toward marine natural product rumphellolide H are presented. Among the synthesized target compounds, the correct structure of linariophyllene A was determined to be the diastereomer of the originally proposed structure with an inverted stereocenter at the secondary alcohol. The proposed structures of linariophyllene B and rumphellolide H were confirmed. However, the correct structure of linariophyllene C was found to be the diastereomer of the originally proposed structure with an inverted stereocenter at the tertiary carbon of the epoxide moiety. The structures of linariophyllenes A-C and rumphellolide H were unequivocally confirmed by single-crystal X-ray diffractometry. The obtained results enabled the proposal of the biosynthetic origins of the aforementioned natural products and bolstered the diversity of available sesquiterpenoids. Linariophyllenes A-C and rumphellolide H were obtained in sufficient amounts to further expand their bioactivity profile and utility as reference standards in future studies of chemical constituents of terrestrial and marine organisms.

Marine Invertebrate Antimicrobial Peptides and Their Potential as Novel Peptide Antibiotics.

Marine invertebrates constantly interact with a wide range of microorganisms in their aquatic environment and possess an effective defense system that has enabled their existence for millions of years. Their lack of acquired immunity sets marine invertebrates apart from other marine animals. Invertebrates could rely on their innate immunity, providing the first line of defense, survival, and thriving. The innate immune system of marine invertebrates includes various biologically active compounds, and specifically, antimicrobial peptides. Nowadays, there is a revive of interest in these peptides due to the urgent need to discover novel drugs against antibiotic-resistant bacterial strains, a pressing global concern in modern healthcare. Modern technologies offer extensive possibilities for the development of innovative drugs based on these compounds, which can act against bacteria, fungi, protozoa, and viruses. This review focuses on structural peculiarities, biological functions, gene expression, biosynthesis, mechanisms of antimicrobial action, regulatory activities, and prospects for the therapeutic use of antimicrobial peptides derived from marine invertebrates.

Peptides from Marine-Derived Fungi: Chemistry and Biological Activities.

Marine natural products are well-recognized as potential resources to fill the pipeline of drug leads to enter the pharmaceutical industry. In this circumstance, marine-derived fungi are one of the unique sources of bioactive secondary metabolites due to their capacity to produce diverse polyketides and peptides with unique structures and diverse biological activities. The present review covers the peptides from marine-derived fungi reported from the literature published from January 1991 to June 2023, and various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, Bentham, ProQuest, and the Marine Pharmacology website, are used for a literature search. This review focuses on chemical characteristics, sources, and biological and pharmacological activities of 366 marine fungal peptides belonging to various classes, such as linear, cyclic, and depsipeptides. Among 30 marine-derived fungal genera, isolated from marine macro-organisms such as marine algae, sponges, coral, and mangrove plants, as well as deep sea sediments, species of Aspergillus were found to produce the highest number of peptides (174 peptides), followed by Penicillium (23 peptides), Acremonium (22 peptides), Eurotium (18 peptides), Trichoderma (18 peptides), Simplicillium (17 peptides), and Beauveria (12 peptides). The cytotoxic activity against a broad spectrum of human cancer cell lines was the predominant biological activity of the reported marine peptides (32%), whereas antibacterial, antifungal, antiviral, anti-inflammatory, and various enzyme inhibition activities ranged from 7% to 20%. In the first part of this review, the chemistry of marine peptides is discussed and followed by their biological activity.

Fascinating Furanosteroids and Their Pharmacological Profile.

This review article delves into the realm of furanosteroids and related isoprenoid lipids derived from diverse terrestrial and marine sources, exploring their wide array of biological activities and potential pharmacological applications. Fungi, fungal endophytes, plants, and various marine organisms, including sponges, corals, molluscs, and other invertebrates, have proven to be abundant reservoirs of these compounds. The biological activities exhibited by furanosteroids and related lipids encompass anticancer, cytotoxic effects against various cancer cell lines, antiviral, and antifungal effects. Notably, the discovery of exceptional compounds such as nakiterpiosin, malabaricol, dysideasterols, and cortistatins has revealed their potent anti-tuberculosis, antibacterial, and anti-hepatitis C attributes. These compounds also exhibit activity in inhibiting protein kinase C, phospholipase A2, and eliciting cytotoxicity against cancer cells. This comprehensive study emphasizes the significance of furanosteroids and related lipids as valuable natural products with promising therapeutic potential. The remarkable biodiversity found in both terrestrial and marine ecosystems offers an extensive resource for unearthing novel biologically active compounds, paving the way for future drug development and advancements in biomedical research. This review presents a compilation of data obtained from various studies conducted by different authors who employed the PASS software 9.1 to evaluate the biological activity of natural furanosteroids and compounds closely related to them. The utilization of the PASS software in this context offers valuable advantages, such as screening large chemical libraries, identifying compounds for subsequent experimental investigations, and gaining insights into potential biological activities based on their structural features. Nevertheless, it is crucial to emphasize that experimental validation remains indispensable for confirming the predicted activities.

Marine Microbial Polysaccharides: An Untapped Resource for Biotechnological Applications.

As the largest habitat on Earth, the marine environment harbors various microorganisms of biotechnological potential. Indeed, microbial compounds, especially polysaccharides from marine species, have been attracting much attention for their applications within the medical, pharmaceutical, food, and other industries, with such interest largely stemming from the extensive structural and functional diversity displayed by these natural polymers. At the same time, the extreme conditions within the aquatic ecosystem (e.g., temperature, pH, salinity) may not only induce microorganisms to develop a unique metabolism but may also increase the likelihood of isolating novel polysaccharides with previously unreported characteristics. However, despite their potential, only a few microbial polysaccharides have actually reached the market, with even fewer being of marine origin. Through a synthesis of relevant literature, this review seeks to provide an overview of marine microbial polysaccharides, including their unique characteristics. In particular, their suitability for specific biotechnological applications and recent progress made will be highlighted before discussing the challenges that currently limit their study as well as their potential for wider applications. It is expected that this review will help to guide future research in the field of microbial polysaccharides, especially those of marine origin.

Functional Properties of Natural Products and Human Health.

Natural products (NPs), broadly defined as chemicals produced by living organisms including microbes, marine organisms, animals, fungi and plants, are widely used as therapeutic agents for treating diseases and maintaining health and "wellness" [...].

Lost world of complex life and the late rise of the eukaryotic crown.

Eukaryotic life appears to have flourished surprisingly late in the history of our planet. This view is based on the low diversity of diagnostic eukaryotic fossils in marine sediments of mid-Proterozoic age (around 1,600 to 800 million years ago) and an absence of steranes, the molecular fossils of eukaryotic membrane sterols1,2. This scarcity of eukaryotic remains is difficult to reconcile with molecular clocks that suggest that the last eukaryotic common ancestor (LECA) had already emerged between around 1,200 and more than 1,800 million years ago. LECA, in turn, must have been preceded by stem-group eukaryotic forms by several hundred million years3. Here we report the discovery of abundant protosteroids in sedimentary rocks of mid-Proterozoic age. These primordial compounds had previously remained unnoticed because their structures represent early intermediates of the modern sterol biosynthetic pathway, as predicted by Konrad Bloch4. The protosteroids reveal an ecologically prominent 'protosterol biota' that was widespread and abundant in aquatic environments from at least 1,640 to around 800 million years ago and that probably comprised ancient protosterol-producing bacteria and deep-branching stem-group eukaryotes. Modern eukaryotes started to appear in the Tonian period (1,000 to 720 million years ago), fuelled by the proliferation of red algae (rhodophytes) by around 800 million years ago. This 'Tonian transformation' emerges as one of the most profound ecological turning points in the Earth's history.

Marine Bioactive Peptides-Structure, Function and Application.

Marine organisms live in harsh marine habitats, causing them to have significantly different and more diverse proteins than those of terrestrial organisms [...].

The Potential of Algae in the Nutricosmetic Sector.

Seaweeds or algae are marine autotrophic organisms. They produce nutrients (e.g., proteins, carbohydrates, etc.) essential for the survival of living organisms as they participate in biochemical processes and non-nutritive molecules (such as dietary fibers and secondary metabolites), which can improve their physiological functions. Seaweed polysaccharides, fatty acids, peptides, terpenoids, pigments, and polyphenols have biological properties that can be used to develop food supplements and nutricosmetic products as they can act as antibacterial, antiviral, antioxidant, and anti-inflammatory compounds. This review examines the (primary and secondary) metabolites produced by algae, the most recent evidence of their effect on human health conditions, with particular attention to what concerns the skin and hair's well-being. It also evaluates the industrial potential of recovering these metabolites from biomass produced by algae used to clean wastewater. The results demonstrate that algae can be considered a natural source of bioactive molecules for well-being formulations. The primary and secondary metabolites' upcycling can be an exciting opportunity to safeguard the planet (promoting a circular economy) and, at the same time, obtain low-cost bioactive molecules for the food, cosmetic, and pharmaceutical industries from low-cost, raw, and renewable materials. Today's lack of methodologies for recovering bioactive molecules in large-scale processes limits practical realization.

Anti-Vibrio potential of natural products from marine microorganisms.

The emergence of drug-resistant Vibrio poses a serious threat to aquaculture and human health, thus there is an urgent need for the discovery of new related antibiotics. Given that marine microorganisms (MMs) are evidenced as important sources of antibacterial natural products (NPs), great attention has been gained to the exploration of potential anti-Vibrio agents from MMs. This review summarizes the occurrence, structural diversity, and biological activities of 214 anti-Vibrio NPs isolated from MMs (from 1999 to July 2022), including 108 new compounds. They were predominantly originated from marine fungi (63%) and bacteria (30%) with great structural diversity, including polyketides, nitrogenous compounds, terpenoids, and steroids, among which polyketides account for nearly half (51%) of them. This review will shed light on the development of MMs derived NPs as potential anti-Vibrio lead compounds with promising applications in agriculture and human health.