Composite antibacterial hydrogels based on two natural products pullulan and ε-poly-l-lysine for burn wound healing.

Antibacterial hydrogels as burn wound dressings are capable of efficaciously defending against bacterial infection and accelerating burn wound healing. Thus far, a large plethora of antibacterial hydrogels have adopted numerous components and intricate preparation processes, yet restricting their practical industrialization applications. Simple and effective preparation methods of antibacterial hydrogels are hence urgently needed. Herein, an easy but efficacious strategy with the employment of two natural products pullulan and ε-poly-l-lysine (ε-PL) was designed to fabricate composite antibacterial hydrogels for burn wound healing for the first time. The hydrogel crosslinking networks were formed through amidation reactions between carboxylated pullulan derivative (CP) and ε-poly-l-lysine hydrochloride (ε-PL·HCl). The resulting hydrogels possessed high transparency, porous structures, tunable gelation time and gel content, relatively low swelling ratios, appropriate self-degradability, proper mechanical properties, strong in vitro bacteriostatic activities, non-cytotoxicity, capacities of facilitating cell migration and excellent hemocompatibility. In the infected burn model of mice, the hydrogels were observed to display prominent in vivo antibacterial activities and enable the acceleration of burn wound healing. We opine the simply and effectively prepared antibacterial hydrogels as promising dressings for burn wound recovery have broad industrialization prospects.

The effect of plant-derived polyphenols on the immune system during aging: a systematic review.

OBJECTIVE: Polyphenols are organic compounds with diverse biological activities such as anti-inflammatory and antioxidant effects, making them important candidates for the development of anti-aging drugs. In this systematic review, we aimed to answer the question: can plant-derived polyphenols have an immunomodulatory effect in experimental models of aging? METHODS: We systematically searched Web of Science, MEDLINE/Pubmed, and Embase to select articles using the following combinations of terms and synonyms: polyphenols, phenols, senescence, aging, and immune. The selected articles were evaluated for reporting quality and risk-of-bias according to standard guidelines. RESULTS: The most used polyphenol was resveratrol, followed by curcumin, salidroside, and gallic acid. These molecules demonstrated an ability to restore immune function both in vitro and in vivo. The mechanism of action was not completely elucidated in these studies, but inhibition of NF-kB signaling, and antioxidant properties seemed to account for the anti-aging effects. All articles included in the review had good quality of reporting but failed to describe an adequate sample size, criteria for inclusion/exclusion, randomization, and blinding. CONCLUSION: We conclude that polyphenols are promising immunomodulatory substances for use in anti-aging therapies. However, more research with standardized analysis is needed to understand the role of these molecules in the prevention or reduction of damage associated with the aging process, as well as to determine the safety profile and consequences of systemic action.

Synergistic Antimicrobial Activity of Biogenic Silver Nanoparticles and Acanthospermum australe Essential Oil against Skin Infection Pathogens.

In response to the steady increase in antimicrobial-resistant strains, the World Health Organisation has emphasised the need to investigate new antimicrobial agents and alternative therapies that improve the spectrum of activity and reduce the dose required, thus improving safety. This study focused on the characterisation of Acanthospermum australe essential oil and green-synthesis silver nanoparticles (AgNP), evaluating their cytotoxicity in human cells, antimicrobial activity and synergistic effect against pathogens causing skin infections. The main components of the essential oil were germacrene A (24.07%), γ-cadinene (21.47%) and trans-caryophyllene (14.97%). Spherical AgNP with a diameter of 15 ± 3 nm were synthesised. The essential oil showed antimicrobial activity against dermatophytes and Malassezia globosa, while AgNP were found to be active against bacteria, yeasts and dermatophytes. Both compounds were found to be primarily non-cytotoxic at the concentrations required to inhibit microbial growth. Furthermore, the combined use of essential oil and AgNP showed a synergistic antimicrobial effect against dermatophytes and M. globosa. In conclusion, the results suggest that the combined use of bioactive compounds from natural sources, such as essential oil and biogenic AgNP, has the potential to improve antimicrobial efficacy against specific skin pathogens, particularly Microsporum canis, Nannizzia gypsea and M. globosa.

Anti-Inflammatory and Cancer-Preventive Potential of Chamomile (Matricaria chamomilla L.): A Comprehensive In Silico and In Vitro Study.

BACKGROUND AND AIM: Chamomile tea, renowned for its exquisite taste, has been appreciated for centuries not only for its flavor but also for its myriad health benefits. In this study, we investigated the preventive potential of chamomile (Matricaria chamomilla L.) towards cancer by focusing on its anti-inflammatory activity. METHODS AND RESULTS: A virtual drug screening of 212 phytochemicals from chamomile revealed ß-amyrin, ß-eudesmol, ß-sitosterol, apigenin, daucosterol, and myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, and flow cytometric determination of reactive oxygen species and mitochondrial membrane potential. An oncobiogram generated through comparison of 91 anticancer agents with known modes of action using the NCI tumor cell line panel revealed significant relationships of cytotoxic chamomile compounds, lupeol, and quercetin to microtubule inhibitors. This hypothesis was verified by confocal microscopy using α-tubulin-GFP-transfected U2OS cells and molecular docking of lupeol and quercetin to tubulins. Both compounds induced G2/M cell cycle arrest and necrosis rather than apoptosis. Interestingly, lupeol and quercetin were not involved in major mechanisms of resistance to established anticancer drugs (ABC transporters, TP53, or EGFR). Performing hierarchical cluster analyses of proteomic expression data of the NCI cell line panel identified two sets of 40 proteins determining sensitivity and resistance to lupeol and quercetin, further pointing to the multi-specific nature of chamomile compounds. Furthermore, lupeol, quercetin, and ß-amyrin inhibited the mRNA expression of the proinflammatory cytokines IL-1ß and IL6 in NF-κB reporter cells (HEK-Blue Null1). Moreover, Kaplan-Meier-based survival analyses with NF-κB as the target protein of these compounds were performed by mining the TCGA-based KM-Plotter repository with 7489 cancer patients. Renal clear cell carcinomas (grade 3, low mutational rate, low neoantigen load) were significantly associated with shorter survival of patients, indicating that these subgroups of tumors might benefit from NF-κB inhibition by chamomile compounds. CONCLUSION: This study revealed the potential of chamomile, positioning it as a promising preventive agent against inflammation and cancer. Further research and clinical studies are recommended.

Exploring the Antiangiogenic and Anti-Inflammatory Potential of Homoisoflavonoids: Target Identification Using Biotin Probes.

Chemical proteomics using biotin probes of natural products have significantly advanced our understanding of molecular targets and therapeutic potential. This review highlights recent progress in the application of biotin probes of homoisoflavonoids for identifying binding proteins and elucidating mechanisms of action. Notably, homoisoflavonoids exhibit antiangiogenic, anti-inflammatory, and antidiabetic effects. A combination of biotin probes, pull-down assays, mass spectrometry, and molecular modeling has revealed how natural products and their derivatives interact with several proteins such as ferrochelatase (FECH), soluble epoxide hydrolase (sEH), inosine monophosphate dehydrogenase 2 (IMPDH2), phosphodiesterase 4 (PDE4), and deoxyhypusine hydroxylase (DOHH). These target identification approaches pave the way for new therapeutic avenues, especially in the fields of oncology and ophthalmology. Future research aimed at expanding the repertoire of target identification using biotin probes of homoisoflavonoids promises to further elucidate the complex mechanisms and develop new drug candidates.

Diversity and potential functional role of phyllosphere-associated actinomycetota isolated from cupuassu (Theobroma grandiflorum) leaves: implications for ecosystem dynamics and plant defense strategies.

Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in Theobroma grandiflorum, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches' broom disease caused by Moniliophthora perniciosa. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu's defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability.

Non-Hereditary Obesity Type Networks and New Drug Targets: An In Silico Approach.

Obesity, a chronic, preventable disease, has significant comorbidities that are associated with a great human and financial cost for society. The aim of the present work is to reconstruct the interactomes of non-hereditary obesity to highlight recent advances of its pathogenesis, and discover potential therapeutic targets. Obesity and biological-clock-related genes and/or gene products were extracted from the biomedical literature databases PubMed, GeneCards and OMIM. Their interactions were investigated using STRING v11.0 (a database of known and predicted physical and indirect associations among genes/proteins), and a high confidence interaction score of >0.7 was set. We also applied virtual screening to discover natural compounds targeting obesity- and circadian-clock-associated proteins. Two updated and comprehensive interactomes, the (a) stress- and (b) inflammation-induced obesidomes involving 85 and 93 gene/gene products of known and/or predicted interactions with an average node degree of 9.41 and 10.8, respectively, were produced. Moreover, 15 of these were common between the two non-hereditary entities, namely, ADIPOQ, ADRB2/3, CCK, CRH, CXCL8, FOS, GCG, GNRH1, IGF1, INS, LEP, MC4R, NPY and POMC, while phelligridin E, a natural product, may function as a potent FOX1-DBD interaction blocker. Molecular networks may contribute to the understanding of the integrated regulation of energy balance/obesity pathogenesis and may associate chronopharmacology schemes with natural products.

Natural Health Products for Anti-Cancer Treatment: Evidence and Controversy.

Natural Health Products (NHPs) have long been considered a valuable therapeutic approach for the prevention and treatment of various diseases, including cancer. However, research on this topic has led to inconclusive and often controversial results. This review aims to provide a comprehensive update of the effects and mechanisms related to the use of NHPs, to describe the results of randomized clinical trials (RCTs) on their effects in cancer patients, and to critically discuss factors influencing clinical outcomes. RCTs available in the literature, even those studying the same NHP, are very heterogeneous in terms of indications, doses, route and timing of administration, and outcomes evaluated. Silymarin, ginsenoside, and vitamin E appear to be useful in attenuating adverse events related to radiotherapy or chemotherapy, and curcumin and lycopene might provide some benefit in patients with prostate cancer. Most RCTs have not clarified whether NHP supplementation provides any real benefit, while harmful effects have been shown in some cases. Overall, the available data suggest that although there is some evidence to support the benefits of NHPs in the management of cancer patients, further clinical trials with the same design are needed before their introduction into clinical practice can be considered.

In Silico and In Vitro Studies of Terpenes from the Fabaceae Family Using the Phenotypic Screening Model against the SARS-CoV-2 Virus.

In 2019, the emergence of the seventh known coronavirus to cause severe illness in humans triggered a global effort towards the development of new drugs and vaccines for the SARS-CoV-2 virus. These efforts are still ongoing in 2024, including the present work where we conducted a ligand-based virtual screening of terpenes with potential anti-SARS-CoV-2 activity. We constructed a Quantitative Structure-Activity Relationship (QSAR) model from compounds with known activity against SARS-CoV-2 with a model accuracy of 0.71. We utilized this model to predict the activity of a series of 217 terpenes isolated from the Fabaceae family. Four compounds, predominantly triterpenoids from the lupane series, were subjected to an in vitro phenotypic screening in Vero CCL-81 cells to assess their inhibitory activity against SARS-CoV-2. The compounds which showed high rates of SARS-CoV-2 inhibition along with substantial cell viability underwent molecular docking at the SARS-CoV-2 main protease, papain-like protease, spike protein and RNA-dependent RNA polymerase. Overall, virtual screening through our QSAR model successfully identified compounds with the highest probability of activity, as validated using the in vitro study. This confirms the potential of the identified triterpenoids as promising candidates for anti-SARS-CoV-2 therapeutics.

Ethnomedicinal Usage, Phytochemistry and Pharmacological Potential of Solanum surattense Burm. f.

Solanum surattense Burm. f. is a significant member of the Solanaceae family, and the Solanum genus is renowned for its traditional medicinal uses and bioactive potential. This systematic review adheres to PRISMA methodology, analyzing scientific publications between 1753 and 2023 from B-on, Google Scholar, PubMed, Science Direct, and Web of Science, aiming to provide comprehensive and updated information on the distribution, ethnomedicinal uses, chemical constituents, and pharmacological activities of S. surattense, highlighting its potential as a source of herbal drugs. Ethnomedicinally, this species is important to treat skin diseases, piles complications, and toothache. The fruit was found to be the most used part of this plant (25%), together with the whole plant (22%) used to treat different ailments, and its decoction was found to be the most preferable mode of herbal drug preparation. A total of 338 metabolites of various chemical classes were isolated from S. surattense, including 137 (40.53%) terpenoids, 56 (16.56%) phenol derivatives, and 52 (15.38%) lipids. Mixtures of different parts of this plant in water-ethanol have shown in vitro and/or in vivo antioxidant, anti-inflammatory, antimicrobial, anti-tumoral, hepatoprotective, and larvicidal activities. Among the metabolites, 51 were identified and biologically tested, presenting antioxidant, anti-inflammatory, and antitumoral as the most reported activities. Clinical trials in humans made with the whole plant extract showed its efficacy as an anti-asthmatic agent. Mostly steroidal alkaloids and triterpenoids, such as solamargine, solanidine, solasodine, solasonine, tomatidine, xanthosaponin A-B, dioscin, lupeol, and stigmasterol are biologically the most active metabolites with high potency that reflects the new and high potential of this species as a novel source of herbal medicines. More experimental studies and a deeper understanding of this plant must be conducted to ensure its use as a source of raw materials for pharmaceutical use.

Dilemmas in Elderly Diabetes and Clinical Practice Involving Traditional Chinese Medicine.

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.

Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases.

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

Skimmianine Showed Neuroprotection against Cerebral Ischemia/Reperfusion Injury.

The aim of this study was to investigate the antioxidant and anti-inflammatory effects of skimmianine on cerebral ischemia-reperfusion (IR) injury. Twenty-four female Wistar albino rats were randomly divided into three groups: Sham, Ischemia-Reperfusion (IR), and IR + Skimmianine (40 mg/kg Skimmianine). Cerebral ischemia was induced using a monofilament nylon suture to occlude the middle cerebral artery for 60 min. Following 23 h of reperfusion, the animals were sacrificed 14 days later. The effects of skimmianine on brain tissue post-IR injury were examined through biochemical and immunochemical analyses. In silico analysis using the Enrichr platform explored skimmianine's potential biological processes involving IBA-1, IL-6, and NF-κB proteins. In the IR group, MDA levels increased, while SOD and CAT antioxidant enzyme activities decreased. In the IR + Skimmianine group, skimmianine treatment resulted in decreased MDA levels and increased SOD and CAT activities. Significant increases in IBA-1 expression were observed in the IR group, which skimmianine treatment significantly reduced, modulating microglial activation. High levels of IL-6 expression were noted in pyramidal neurons, vascular structures, and neuroglial cells in the IR group; skimmianine treatment reduced IL-6 expression, demonstrating anti-inflammatory effects. Increased NF-κB expression was observed in neurons and blood vessels in the gray and white matter in the IR group; skimmianine treatment reduced NF-κB expression. Gene Ontology results suggest skimmianine impacts immune and inflammatory responses via IBA-1 and IL-6, with potential effects on estrogen mechanisms mediated by NF-κB. Skimmianine may be a potential therapeutic strategy due to its antioxidant and anti-inflammatory effects on cerebral IR injury.

Ganoderma pfeifferi Bres. and Ganoderma resinaceum Boud. as Potential Therapeutic Agents: A Comparative Study on Antiproliferative and Lipid-Lowering Properties.

Medicinal mushrooms, especially Ganoderma species, hold immense promise for the production of a wide range of bioactive compounds with various effects. The biochemical potential of indigenous fungal strains, specific to a region, could play a critical role in the continuous search for novel strains with superior activities on a global scale. This research focused on the ethanolic (EtOH) and hot-water (H2O) extracts of fruiting bodies of two wild-growing Ganoderma species: G. pfeifferi and G. resinaceum, with the aim of assessing their nutritional (total carbohydrate content-TCC) and mineral composition in relation to bioactive properties: antioxidant, antiproliferative and lipid-lowering. Atomic absorption spectrophotometry (AAS) revealed that G. pfeifferi is a promising source of minerals that are essential for numerous physiological functions in the human body like bone health and muscle and nerve function, with Ca (4.55 ± 0.41 mg/g d.w.) and Mg (1.33 ± 0.09 mg/g d.w.) being the most abundant macroelement present. Zn, Mn, and Cr were particularly notable, with concentrations ranging from 21.49 to 41.70 mg/kg d.w. The EtOH extract of G. pfeifferi demonstrated significantly elevated levels of TCC, essential macromolecules for energy and structural functions in the body, with higher quantities of all three standard carbohydrates detected in this type of extract. Similar to the revealed composition, the same species, G. pfeifferi, stood out as the most prominent antioxidant agent, with the H2O extract being stronger than EtOH in the ABTS assay (86.85 ± 0.67 mg TE/g d.w.), while the EtOH extract displayed the highest anti-OH• scavenging ability (IC50 = 0.18 ± 0.05 µg/mL) as well as the most notable reducing potential among all. The highest antiproliferative effect against the breast cancer cell line (MCF-7), were demonstrated by the H2O extracts from G. resinaceum with the most pronounced activity after 24 h (IC50 = 4.88 ± 0.50 µg/mL), which surpasses that of the standard compound, ellagic acid (IC50 = 33.94 ± 3.69 µg/mL). Administration of both Ganoderma extracts mitigated diabetic lipid disturbances and exhibited potential renal and hepatic protection in vivo on white Wistar rats by the preservation of kidney function parameters in G. resinaceum H2O pre-treatment (urea: 6.27 ± 0.64 mmol/L, creatinine: 50.00 ± 6.45 mmol/L) and the reduction in ALT levels (17.83 ± 3.25 U/L) compared to diabetic control groups treated with saline (urea: 46.98 ± 6.01 mmol/L, creatinine: 289.25 ± 73.87 mmol/L, and ALT: 60.17 ± 9.64 U/L). These results suggest that pre-treatment with G. resinaceum H2O extracts may have potential antidiabetic properties. In summary, detected microelements are vital for maintaining overall health, supporting metabolic processes, and protecting against various chronic diseases. Further research and dietary assessments could help determine the full potential and applications of the two underexplored Ganoderma species native to Serbia in nutrition and health supplements.

Effects of Marine Natural Products on Liver Diseases.

The prevention and treatment of liver disease, a class of disease that seriously threatens human health, has always been a hot topic of medical research. In recent years, with the in-depth exploration of marine resources, marine natural products have shown great potential and value in the field of liver disease treatment. Compounds extracted and isolated from marine natural products have a variety of biological activities such as significant antiviral properties, showing potential in the management of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), protection of the liver from fibrosis, protection from liver injury and inhibition of the growth of hepatocellular carcinoma (HCC). This paper summarizes the progress of research on marine natural products for the treatment of liver diseases in the past decade, including the structural types of active substances from different natural products and the mechanisms underlying the modulation of different liver diseases and reviews their future prospects.

Proof of Concept of Natural and Synthetic Antifouling Agents in Coatings.

Marine biofouling, caused by the deposition and accumulation of marine organisms on submerged surfaces, represents a huge concern for the maritime industries and also contributes to environmental pollution and health concerns. The most effective way to prevent this phenomenon is the use of biocide-based coatings which have proven to cause serious damage to marine ecosystems. Several research groups have focused on the search for new environmentally friendly antifoulants, including marine and terrestrial natural products and synthetic analogues. Some of these compounds have been incorporated into marine coatings and display interesting antifouling activities caused by the interference with the biofilm-forming species as well as by the inhibition of the settlement of macroorganisms. This review highlights the proof-of-concept studies of emerging natural or synthetic antifouling compounds in coatings, from lab-made to commercial ones, performed between 2019 and 2023 and their results in the field or in in vivo laboratorial tests.

Identification of Axinellamines A and B as Anti-Tubercular Agents.

Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library (n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A (1) and B (2). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC90) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.

Total Synthesis and Biological Profiling of Putative (±)-Marinoaziridine B and (±)-N-Methyl Marinoaziridine A.

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8.

Anti-Biofilm Extracts and Molecules from the Marine Environment.

Pathogenic bacteria and their biofilms are involved in many diseases and represent a major public health problem, including the development of antibiotic resistance. These biofilms are known to cause chronic infections for which conventional antibiotic treatments are often ineffective. The search for new molecules and innovative solutions to combat these pathogens and their biofilms has therefore become an urgent need. The use of molecules with anti-biofilm activity would be a potential solution to these problems. The marine world is rich in micro- and macro-organisms capable of producing secondary metabolites with original skeletons. An interest in the chemical strategies used by some of these organisms to regulate and/or protect themselves against pathogenic bacteria and their biofilms could lead to the development of bioinspired, eco-responsible solutions. Through this original review, we listed and sorted the various molecules and extracts from marine organisms that have been described in the literature as having strictly anti-biofilm activity, without bactericidal activity.