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Molecules (Basel, Switzerland) Mar 2024Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and...
Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at -5 and -9 yielded makaluvamine J and several analogs. A structure-activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at -9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at -5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog showed potent and selective cytotoxicity (IC = 0.029 µM, selective index = 13.1), exceeding those of natural products.
Topics: Animals; Humans; Pyrroloiminoquinones; Structure-Activity Relationship; Porifera; Antineoplastic Agents; Alkaloids
PubMed: 38543025
DOI: 10.3390/molecules29061389 -
Acta Pharmacologica Sinica Jul 2024Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist....
Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.
Topics: Animals; Lipid Metabolism; Neuroprotective Agents; Homeostasis; Porifera; Mice; Mice, Inbred C57BL; Autophagy; Male; Parkinson Disease; Polyketides; Humans
PubMed: 38538717
DOI: 10.1038/s41401-024-01259-y -
Marine Drugs Mar 2024Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are...
Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time.
Topics: Humans; Animals; Porifera; Polysaccharides; Glycosaminoglycans; Anticoagulants; Blood Coagulation; Sulfates
PubMed: 38535480
DOI: 10.3390/md22030139 -
Marine Drugs Mar 2024The Verongida order comprises several sponge families, such as Aplysinellidae, Aplysinidae, Ianthellidae, and Pseudoceratinidae, reported for producing... (Review)
Review
The Verongida order comprises several sponge families, such as Aplysinellidae, Aplysinidae, Ianthellidae, and Pseudoceratinidae, reported for producing bromotyrosine-derived compounds. First identified in 1913, bromotyrosine derivatives have since captivated interest notably for their antitumor and antimicrobial properties. To date, over 360 bromotyrosine derivatives have been reported. Our review focuses specifically on bromotyrosine derivatives newly reported from 2004 to 2023, by summarizing current knowledge about their chemical diversity and their biological activities.
Topics: Humans; Animals; Bandages; Porifera; Tyrosine
PubMed: 38535473
DOI: 10.3390/md22030132 -
Marine Drugs Feb 2024Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the... (Review)
Review
Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
Topics: Animals; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Biological Products; Apoptosis; Porifera
PubMed: 38535442
DOI: 10.3390/md22030101 -
Marine Drugs Feb 2024An unreported prenylated indole derivative hydroxytakakiamide () was isolated, together with the previously described ergosterol (), ergosterol acetate (), and...
Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.
An unreported prenylated indole derivative hydroxytakakiamide () was isolated, together with the previously described ergosterol (), ergosterol acetate (), and (3)-3-(1-indol-3-ylmethyl)-3, 4-dihydro-1-1,4-benzodiazepine-2,5-dione (), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, MMERU 23. The structure of was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and were evaluated, together with acetylaszonalenin () and helvolic acid (), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while , , and displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor , , and affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of , , and were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than on the three antinociceptive targets. On the other hand, has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.
Topics: Animals; Mice; Molecular Docking Simulation; Fungi; Porifera; Acetic Acid; Ergosterol; Analgesics; Acetates; Aspergillus; Fusidic Acid
PubMed: 38535438
DOI: 10.3390/md22030097 -
Molecular Ecology Apr 2024Fundamental to holobiont biology is recognising how variation in microbial composition and function relates to host phenotypic variation. Sponges often exhibit...
Fundamental to holobiont biology is recognising how variation in microbial composition and function relates to host phenotypic variation. Sponges often exhibit considerable phenotypic plasticity and also harbour dense microbial communities that function to protect and nourish hosts. One of the most prominent sponge genera on Caribbean coral reefs is Agelas. Using a comprehensive set of morphological (growth form, spicule), chemical and molecular data on 13 recognised species of Agelas in the Caribbean basin, we were able to define only five species (=clades) and found that many morphospecies designations were incongruent with phylogenomic and population genetic analyses. Microbial communities were also strongly differentiated between phylogenetic species, showing little evidence of cryptic divergence and relatively low correlation with morphospecies assignment. Metagenomic analyses also showed strong correspondence to phylogenetic species, and to a lesser extent, geographical and morphological characters. Surprisingly, the variation in secondary metabolites produced by sponge holobionts was explained by geography and morphospecies assignment, in addition to phylogenetic species, and covaried significantly with a subset of microbial symbionts. Spicule characteristics were highly plastic, under greater impact from geographical location than phylogeny. Our results suggest that while phenotypic plasticity is rampant in Agelas, morphological differences within phylogenetic species affect functionally important ecological traits, including the composition of the symbiotic microbial communities and metabolomic profiles.
Topics: Animals; Phylogeny; Agelas; Caribbean Region; West Indies; Coral Reefs; Porifera
PubMed: 38529721
DOI: 10.1111/mec.17321 -
The Journal of Antibiotics Jun 2024Okichromanone (1), a new chromanone, was isolated from the culture extract of a sponge-derived actinomycete Microbispora, along with known 1-hydroxyphenazine (2)....
Okichromanone (1), a new chromanone, was isolated from the culture extract of a sponge-derived actinomycete Microbispora, along with known 1-hydroxyphenazine (2). Compound 1 was elucidated to exist as a mixture of two isomeric structures (1a and 1b) at a ratio of nearly 3:2. Compounds 1 and 2 showed anti HSV-I activity with IC values 40 and 86 μM, respectively, and anti HSV-II activity with IC values 59 and 123 μM, respectively.
Topics: Animals; Actinobacteria; Antiviral Agents; Chlorocebus aethiops; Chromones; Herpesvirus 1, Human; Inhibitory Concentration 50; Molecular Structure; Porifera; Vero Cells
PubMed: 38519549
DOI: 10.1038/s41429-024-00718-2 -
PloS One 2024According to some cohort studies, an association exists between acute intermittent porphyria (AIP) and liver cancer. However, establishing a definitive causal...
PURPOSE
According to some cohort studies, an association exists between acute intermittent porphyria (AIP) and liver cancer. However, establishing a definitive causal relationship between porphyria and hepatocellular carcinoma (HCC) remains challenging. Prexisting studies regarding porphyria biomarkers and alcohol-related hepatocellular carcinoma (AR-HCC) make possible an entry point. In this study, we aimed to investigate the causal relationships between biomarkers of two types of porphyria, AIP and congenital erythropoietic porphyria (CEP), and AR-HCC.
METHODS
Single-nucleotide polymorphisms (SNPs) associated with porphobilinogen deaminase (PBGD) and uroporphyrinogen-III synthase (UROS), along with outcome data on AR-HCC, were extracted from public genome-wide association studies (GWAS). The GWAS data were then used to explore the potential causal relationships via a two-sample Mendelian randomization (MR) analysis. The effect estimates were calculated using the random-effect inverse-variance-weighted (IVW) method. Additionally, the Cochrane's Q test, MR-Egger test, and leave-one-out analysis were conducted to detect heterogeneity and pleiotropy in the MR results.
RESULTS
Using the IVW method as the primary causal effects model in the MR analyses, we found that both PBGD (effect estimate = 1.51; 95% CI, from 1.08 to 2.11, p = 0.016) and UROS (effect estimate = 1.53; 95% CI, from 1.08 to 2.18, p = 0.018) have a significant causal effect on AR-HCC.
CONCLUSION
Our findings revealed a causal effect of both PBGD and UROS on AR-HCC, suggesting that both AIP and CEP have a causal association with AR-HCC.
Topics: Humans; Animals; Carcinoma, Hepatocellular; Liver Neoplasms; Genome-Wide Association Study; Mendelian Randomization Analysis; Porphyrias; Porphyria, Acute Intermittent; Biomarkers; Porifera
PubMed: 38507434
DOI: 10.1371/journal.pone.0299536 -
Journal of Natural Products Apr 2024HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge sp. Its structure was determined as a tripeptide, named neopetromin...
HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge sp. Its structure was determined as a tripeptide, named neopetromin (), composed of two tyrosine and one tryptophan residues with a heteroaromatic C-N cross-link between side chains. The absolute configuration of amino acids was determined using Marfey's method after ozonolysis and hydrolysis of . Compound promoted vacuole fragmentation in an actin-independent manner in tobacco BY-2 cells.
Topics: Animals; Molecular Structure; Porifera; Nicotiana; Vacuoles; Peptides, Cyclic; Marine Biology; Oligopeptides; Chromatography, High Pressure Liquid; Tryptophan
PubMed: 38503712
DOI: 10.1021/acs.jnatprod.4c00158