Potential of Polar Lipids Isolated from the Marine Sponge Haliclona (Halichoclona) vansoesti against Melanoma.

Marine sponges represent a good source of natural metabolites for biotechnological applications in the pharmacological, cosmeceutical, and nutraceutical fields. In the present work, we analyzed the biotechnological potential of the alien species Haliclona (Halichoclona) vansoesti de Weerdt, de Kluijver & Gomez, 1999, previously collected in the Mediterranean Sea (Faro Lake, Sicily). The bioactivity and chemical content of this species has never been investigated, and information in the literature on its Caribbean counterpart is scarce. We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 µg mL-1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Through orthogonal SPE fractionations, we identified two active sphingoid-based lipid classes, also characterized by nuclear magnetic resonance and mass spectrometry, as the main components of two active fractions. Overall, our findings provide the first evaluation of the anti-cancer potential of polar lipids isolated from the marine sponge H. (Halichoclona) vansoesti, which may lead to new lead compounds with biotechnological applications in the pharmaceutical field.

Isolation Techniques, Structural Characteristics, and Pharmacological Effects of Phellinus Polysaccharides: A Review.

Phellinus is a precious perennial medicinal fungus. Its polysaccharides are important bioactive components, and their chemical composition is complex. The polysaccharides are mainly extracted from the fruiting body and mycelium. The yield of the polysaccharides is dependent on the extraction method. They have many pharmacological activities, such as antitumor, immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory, etc. They are also reported to show minor toxic and side effects. Many studies have reported the anticancer activity of Phellinus polysaccharides. This review paper provides a comprehensive examination of the current methodologies for the extraction and purification of Phellinus polysaccharides. Additionally, it delves into the structural characteristics, pharmacological activities, and mechanisms of action of these polysaccharides. The primary aim of this review is to offer a valuable resource for researchers, facilitating further studies on Phellinus polysaccharides and their potential applications.

Polysaccharides from Porphyra haitanensis: A Review of Their Extraction, Modification, Structures, and Bioactivities.

Porphyra haitanensis (P. haitanensis), an important food source for coastal residents in China, has a long history of medicinal and edible value. P. haitanensis polysaccharides are some of the main active ingredients in P. haitanensis. It is worth noting that P. haitanensis polysaccharides have a surprising and satisfactory biological activity, which explains the various benefits of P. haitanensis to human health, such as anti-oxidation, immune regulation, anti-allergy, and anticancer properties. Hence, a systematic review aimed at comprehensively summarizing the recent research advances in P. haitanensis polysaccharides is necessary for promoting their better understanding. In this review, we systematically and comprehensively summarize the research progress on the extraction, purification, structural characterization, modification, and biological activity of P. haitanensis polysaccharides and address the shortcomings of the published research and suggest area of focus for future research, providing a new reference for the exploitation of polysaccharides from P. haitanensis in the fields of medicine and functional foods.

Structure and in vitro antiproliferative activity against breast cancer cells of the cell-wall polysaccharide from the marine bacterium Kangiella japonica KMM 3899T.

Kangiella japonica KMM 3899T is a Gram-negative bacterium isolated from a sandy sediment sample collected from the Sea of Japan. Here the results of the structure and the biological activity against breast cancer cells of the cell-wall polysaccharide from K. japonica KMM 3899T have been described. The structure of the repeating unit of the polysaccharide was elucidated using chemical analysis and NMR spectroscopy: →4)-α-L-GalpNAc3AcA-(1 â†’ 3)-α-D-GlcpNAc-(1 â†’ 4)-ß-D-GlcpNAc3NAcAN-(1→. The cell-wall polysaccharide had an antiproliferative effect against T-47D cells. Flow cytometric and Western blot analysis revealed that the polysaccharide induced S phase arrest and mitochondrial-dependent apoptosis.

Konjac glucomannan: A comprehensive review of its extraction, health benefits, and pharmaceutical applications.

Konjac glucomannan (KG) is a dietary fiber hydrocolloid derived from Amorphophallus konjac tubers and is widely utilized as a food additive and dietary supplement. As a health-conscious choice, purified KG, along with konjac flour and KG-infused diets, have gained widespread acceptance in Asian and European markets. An overview of the chemical composition and structure of KG is given in this review, along with thorough explanations of the processes used in its extraction, production, and purification. KG has been shown to promote health by reducing glucose, cholesterol, triglyceride levels, and blood pressure, thereby offering significant weight loss advantages. Furthermore, this review delves into the extensive health benefits and pharmaceutical applications of KG and its derivatives, emphasizing its prebiotic, anti-inflammatory, and antitumor activities. This study highlights how these natural polysaccharides can positively influence health, underscoring their potential in various biomedical applications.

Cellulamides: A New Family of Marine-Sourced Linear Peptides from the Underexplored Cellulosimicrobium Genus.

Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.

New Meroterpenoids and α-Pyrone Derivatives Isolated from the Mangrove Endophytic Fungal Strain Aspergillus sp. GXNU-Y85.

Two new meroterpenoids, aspergienynes O and P (1 and 2), one new natural compound, aspergienyne Q (3), and a new α-pyrone derivative named 3-(4-methoxy-2-oxo-2H-pyran-6-yl)butanoic acid (4) were isolated from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85, along with five known compounds (5-9). The absolute configurations of those new isolates were confirmed through extensive analysis using spectroscopic data (HRESIMS, NMR, and ECD). The pharmacological study of the anti-proliferation activity indicated that isolates 5 and 9 displayed moderate inhibitory effects against HeLa and A549 cells, with the IC50 values ranging from 16.6 to 45.4 µM.

Dicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/ß-Catenin Signaling Pathway.

Overwhelming evidence points to an aberrant Wnt/ß-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/ß catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/ß-catenin signaling by inhibiting ß-catenin transcriptional activity and abrogating ß-catenin translocated to the nucleus; down-regulating the transcription level of ß-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-ß, ß-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-ß expression, which indicates that DD-9 stabilized the ß-catenin degradation complex, thereby inducing ß-catenin degradation and inactivation of the Wnt/ß-catenin pathway. The possible interaction between DD-9 and ß-catenin and GSK3-ß protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-ß-mediated crosstalk with the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.

Cytotoxic Pentaketide-Sesquiterpenes from the Marine-Derived Fungus Talaromyces variabilis M22734.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

Molecular expression, purification and structural characterization of recombinant L-Glutaminase from Streptomyces roseolus.

The present research reports the anti-cancer potential of recombinant L-Glutaminase from Streptomyces roseolus. L-Glutaminase gene was synthesized by codon-optimization, cloned and successfully expressed in E. coli BL21 (DE3). Affinity purified recombinant L-Glutaminase revealed a molecular mass of 32 kDa. Purified recombinant L-Glutaminase revealed stability at pH 7.0-8.0 with optimum activity at 70 °C further indicating its thermostable nature based on thermodynamic characterization. Recombinant L-Glutaminase exhibited profound stability in the presence of several biochemical parameters and demonstrated its metalloenzyme nature and was also found to be highly specific towards favorable substrate (l-Glutamine) based on kinetics. It demonstrated antioxidant property and pronounced cytotoxic effect against breast cancer (MCF-7 cell lines) in a dose dependent behavior with IC50 of 40.68 µg/mL. Matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis of desired mass peaks ascertained the recombinant L-Glutaminase identity. N-terminal amino acid sequence characterization through Edman degradation revealed highest resemblance for L-glutaminase within the Streptomyces sp. family. The purified protein was characterized structurally and functionally by employing spectroscopic methods like Raman, circular dichroism and nuclear magnetic resonance. The thermostability was assessed by thermogravimetric analysis. The outcomes of the study, suggests the promising application of recombinant L-Glutaminase as targeted therapeutic candidate for breast cancer.

Peniapyrones A-I, Cytotoxic Tricyclic-Fused α-Pyrone Derivatives from an Endophytic Penicillium brefeldianum F4a.

Five cyclopenta[d]pyrano[4,3-b]pyran-1,7(6H)-dione 6/6/5-fused tricyclic ring system containing metabolites peniapyrones A-E (1-5), and four previously undescribed cyclopenta[4,5]furo[3,2-c]pyran-1-one 6/5/5-fused tricyclic ring system containing compounds peniapyrones F-I (6-9), were isolated from the endophytic Penicillium brefeldianum F4a. Their structures, including absolute configurations, were determined through spectroscopic analysis and quantum chemical calculations. Peniapyrones D (4) and E (5) were a pair of diastereoisomers. Compounds 1, 3, and 5-9 showed cytotoxic activity against AsPC-1, CRL-2234, and MCF-7 cancer cell lines. Compounds 1, 3, 6, 8, and 9 inhibited the Kirsten rat sarcoma viral oncogene homologue (KRAS) mutant AsPC-1 cell line.

Ergone Derivatives from the Deep-Sea-Derived Fungus Aspergillus terreus YPGA10 and 25,28-Dihydroxyergone-Induced Apoptosis in Human Colon Cancer SW620 Cells.

Ten new ergone derivatives (1-10) and five known analogues (11-15) were isolated from the deep-sea-derived fungus Aspergillus terreus YPGA10. The structures including the absolute configurations were established by detailed analysis of the NMR spectroscopic data, HRESIMS, ECD calculation, and coupling constant calculation. All the structures are characterized by a highly conjugated 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one nucleus. Structurally, compound 2 bearing a 15-carbonyl group and compounds 5-7 possessing a 15ß-OH/OCH3 group are rarely encountered in ergone derivatives. Bioassay results showed that compounds 1 and 11 demonstrated cytotoxic effects on human colon cancer SW620 cells with IC50 values of 8.4 and 3.1 µM, respectively. Notably, both compounds exhibited negligible cytotoxicity on the human normal lung epithelial cell BEAS-2B. Compound 11 was selected for preliminary mechanistic study and was found to inhibit cell proliferation and induce apoptosis in human colon cancer SW620 cells. In addition, compound 1 displayed cytotoxic activity against five human leukemia cell lines with IC50 values ranging from 5.7 to 8.9 µM. Our study demonstrated that compound 11 may serve as a potential candidate for the development of anticolorectal cancer agents.

Discovery of Kebanmycins with Antibacterial and Cytotoxic Activities from the Mangrove-Derived Streptomyces sp. SCSIO 40068.

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain Streptomyces sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A-D (1-4) and two known analogues FD-594 (5) and the aglycon (6). The structures of 1-6 were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. 1-3 featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster (keb) was identified in Streptomyces sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar-O-methyltransferase, leading to a proposed biosynthetic route to 1-6. This study paves the way to further investigate 1 as a potential lead compound.

UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

A fungal polysaccharide from Fomitopsis officinalis as a multi-target molecule to combat cancer.

Some macrofungi have a long history of being used as traditional or folk medicines, making significant contributions to human health. To discover bioactive molecules with potential anticancer properties, a homogeneous heteropolysaccharide (FOBP90-1) was purified from the medicinal macrofungus Fomitopsis officinalis. FOBP90-1 was found to have a molecular weight of 2.87 × 104 g/mol and mainly consist of →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, →6)-ß-d-Glcp-(1→, α-d-Manp-(1→, and 3-O-Me-α-l-Fucp-(1→ according to UV, FT-IR, methylation analysis, and NMR data. In addition to its structural properties, FOBP90-1 displayed anticancer activity in zebrafish models. The following mechanistic analysis discovered that the in vivo antitumor effect was linked to immune activation and angiogenesis inhibition. These effects were mediated by the interactions of FOBP90-1 with TLR-2, TLR-4, PD-L1, and VEGFR-2, as determined through a series of experiments involving cells, transgenic zebrafish, molecular docking simulations, and surface plasmon resonance (SPR). All the experimental findings have demonstrated that FOBP90-1, a purified fungal polysaccharide, is expected to be utilized as a cancer treatment agent.

Prospecting bioactivity in Antarctic algae: A review of extracts, isolated compounds and their effects.

Algae and its metabolites have been a popular subject of research in numerous fields over the years. Various reviews have been written on algal bioactive components, but a specific focus on Antarctic-derived algae is seldom reviewed. Due to the extreme climate conditions of Antarctica, it is hypothesized that the acclimatized algae may have given rise to a new set of bioactive compounds as a result of adaptation. Although most studies done on Antarctic algae are based on ecological and physiological studies, as well as in the field of nanomaterial synthesis, some studies point out the potential therapeutic properties of these compounds. As an effort to shed light on a different application of Antarctic algae, this review focuses on evaluating its different medicinal properties, including antimicrobial, anticancer, antioxidative, anti-inflammatory, and skin protective effects.

Screening and separation of natural anticancer active ingredients related to phospholipase C.

Based on the specific binding of drug molecules to cell membrane receptors, a screening and separation method for active compounds of natural products was established by combining phospholipase C (PLC) sensitized hollow fiber microscreening by a solvent seal with high-performance liquid chromatography technology. In the process, the factors affecting the screening were optimized. Under the optimal screening conditions, we screened honokiol (HK), magnolol (MG), negative control drug carbamazepine, and positive control drug amentoflavone, the repeatability of the method was tested. The PLC activity was determined before and after the screening. Experimental results showed that the sensitization factors of PLC of HK and MG were 61.0 and 48.5, respectively, and amentoflavone was 15.0, carbamazepine could not bind to PLC. Moreover, the molecular docking results were consistent with this measurement, indicating that HK and MG could be combined with PLC, and they were potential interacting components with PLC. This method used organic solvent to seal the PLC greatly ensuring the activity, so this method had the advantage of integrating separation, and purification with screening, it not only exhibited good reproducibility and high sensitivity but was also suitable for screening the active components in natural products by various targets in vitro.

Three new nonenes from culture broth of marine-derived fungus Albifimbria verrucaria and their cytotoxic and anti-viral activities.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner.

Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells.

Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C-E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 µM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.