New Secondary Metabolites of Mangrove-Associated Strains.

Positioned at the dynamic interface between terrestrial and marine realms, mangroves embody a vibrant tapestry of biodiversity, encompassing an array of plants, animals, and microorganisms. These microbial inhabitants of mangrove habitats have emerged as a pivotal resource for antimicrobials and a plethora of pharmaceutically valuable compounds, spanning enzymes, antineoplastic agents, pesticides, immunosuppressants, and immunomodulators. This review delves into the recent landscape (January 2021 to May 2024, according to the time of publication) of novel secondary metabolites isolated from mangrove-associated microorganisms, analyzing 41 microbial strains that collectively yielded 165 distinct compounds. Our objective is to assess the productivity and potential of natural products derived from microbial populations within mangrove ecosystems in recent times. Notably, fungi stand out as the preeminent contributors to the emergence of these novel natural products, underscoring their pivotal role in the bioprospecting endeavors within these unique environments.

Proangiogenic Azaphilones from the Marine-Derived Fungus Neopestalotiopsis sp. HN-1-6.

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1-3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5-17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 µM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 µg/mL to 256 µg/mL.

Role of myeloid-derived suppressor cells in chronic brucellosis.

Introduction: Human brucellosis, a Brucella infection caused most common zoonosis in the world, remains a serious public health burden in China. Brucella chronic infection always causes immunosuppressive status and results in severe organ or tissue damages. The aim of this work was to study the role of the myeloid-derived suppressor cells (MDSCs) in human chronic brucellosis. Methods: Fifty cases of chronic brucellosis and 40 healthy individual controls were enrolled in this study. We analyzed the frequency and subsets of MDSCs in PBMC between the chronic brucellosis and healthy control groups by flow cytometry. Furthermore, we also measured the inflammatory-related cytokines in serum samples and the MDSCs inhibition ability to the proliferation of T cells in vitro. Results: We found that the frequency of MDSCs in peripheral blood and the level of IL-6 and IL-10 Th2 cytokines and Arginase-1 were significantly increased in chronic brucellosis patients. In addition, we also found that the T cell function was suppressed in vitro by co-culturing with MDSCs from brucellosis patients. Conclusion: Our study described an increase of immunosuppressive MDSCs in peripheral blood of chronic brucellosis patients. These results contribute to the understanding of Brucella persistent infection, which may provide an insight for effective treatment of chronic brucellosis patients in clinical practice.

Diverse indole-diterpenoids with protein tyrosine phosphatase 1B inhibitory activities from the marine coral-derived fungus Aspergillus sp. ZF-104.

Eight previously undescribed indole-diterpenoids named penerpenes O-V (1-8), together with seven known analogues (9-14), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Their structures including the absolute configurations of these compounds were assigned on the basis of spectroscopic data and ECD analysis along with quantum ECD and NMR calculations. Compounds 4 and 5 bear rare indolin-2-one units in their structures and 6 bears a reconstructed novel skeleton in which the indole ring and the terpenoid substructure are cleaved before they are reconnected through the nitrogen atom. Compounds 1, 2, 7, and 10 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activities comparable to that of the positive control NaVO3.

Prenylated indole-terpenoids with antidiabetic activities from Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne.

Finding novel and effective suppression of hepatic glucagon response antidiabetic compounds is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. In this study, four new prenylated indole-terpenoids (1-4), named encindolenes I-L, as well as a known analogue (5), were isolated from the fungus Penicillium sp. HFF16from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the antidiabetic activity assay, compounds 1-5 could inhibit glucagon-induced hepatic glucose output with EC50 values of 67.23, 102.1, 49.46, 25.20, and 35.96 µM, respectively, and decrease the intracellular cAMP contents in primary hepatocytes.

Pleiotropic effects of a mitochondrion-targeted glutathione reductase inhibitor on restraining tumor cells.

Mitochondria has been identified as a target for tumor therapy. Agents preferentially concentrated in mitochondria may exert more potent antitumor effects by interfering with the normal function of mitochondria. Glutathione reductase (GR) in mitochondria is a crucial antioxidant enzyme to maintain mitochondrial function, and has been recognized as an important target for the development of anticancer drugs. Herein, we present a triphenylphosphonium-modified anticancer agent, MT-1, which can preferentially accumulate in mitochondria and bind to GR by covalent binding manner. As a result, morphology and function of mitochondria were severely damaged, as well as cellular energy supply was severely impeded due to the simultaneously inhibition against mitochondrial respiration and glycolysis. Moreover, MT-1 was found to bind to a completely new site of GR (C278) that has never considered as binding site of inhibitors before. This new binding mode led to the change of GR structure, which affected the stability of the transition state of the catalytic process, and finally led to the inhibition of GR activity. Thus, current study provided a potentially novel tumor therapeutic strategy by targeting novel sites of GR in mitochondrion.

Tetrazine bioorthogonal chemistry makes nanotechnology a powerful toolbox for biological applications.

Bioorthogonal chemistry enables researchers to manipulate bioactive molecules in living systems. These highly selective and biocompatible reactions can be carried out in various complex environments. Over the past two decades, a considerable number of strides have been made to expand the capacities of bioorthogonal chemistry coupled with the aim to fine-tune present reactions for specific applications. The good points of bioorthogonal chemistry have pushed material chemists to integrate bioorthogonal chemistry with nanotechnologies to broaden the biological applications of nanomaterials. Notably, bioorthogonal nanotechnologies fundamentally rely on, more than half, according to our investigation, tetrazine bioorthogonal chemistry (TBC) to function as bioorthogonal handles to react with target agents owing to the extremely rapid kinetics and high selectivities of TBC. Its utilization in combination with nanotechnologies has led to developments in various areas of biomedicine, such as in situ drug activation and targeted delivery, bioimaging and biosensing, and the understanding of cell-biomolecule interactions. Given the fantastic past achievements and the rapid developments in tetrazine bioorthogonal technologies, the future is certainly very bright.

Carotane sesquiterpenoids A-G from the desert endophytic fungus Fusarium sp. HM 166.

Seven undescribed carotane sesquiterpenoids named fusanoids A-G (1-7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4-9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1R132h mutant.

Phenethoxy Derivatives with Anti-inflammatory Activities from the Betelnut Endophytic Trichoderma asperellum G10.

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).

Identification and Comprehensive Analysis of FREM2 Mutation as a Potential Prognostic Biomarker in Colorectal Cancer.

Gene mutations play an important role in tumor progression. This study aimed to identify genes that were mutated in colorectal cancer (CRC) and to explore their biological effects and prognostic value in CRC patients. We performed somatic mutation analysis using data sets from The Cancer Genome Atlas and International Cancer Genome Consortium, and identified that FREM2 had the highest mutation frequency in patients with colon adenocarcinoma (COAD). COAD patients were divided into FREM2-mutated type (n = 36) and FREM2-wild type (n = 278), and a Kaplan-Meier survival curve was generated to perform prognostic analysis. A FREM2-mutation prognosis model was constructed using random forest method, and the performance of the model was evaluated using receiver operating characteristic curve. Next, the random forest method and Cox regression analysis were used to construct a prognostic model based on the gene expression data of 36 FREM2-mutant COAD patients. The model showed a high prediction accuracy (83.9%), and 13 prognostic model characteristic genes related to overall survival were identified. Then, the results of tumor mutation burden (TMB) and microsatellite instability (MSI) analyses revealed significant differences in TMB and MSI among the risk scores of different prognostic models. Differentially expressed genes were identified and analyzed for functional enrichment and immune infiltration. Finally, 30 samples of CRC patients were collected for immunohistochemical staining to analyze the FREM2 expression levels, which showed that FREM2 was highly expressed in tumor tissues. In conclusion, CRC patients had a high level of FREM2 mutations associated with a worse prognosis, which indicated that FREM2 mutations may be potential prognostic markers in CRC.

A new picrotoxane-type sesquiterpene from Dendrobium nobile Lindl.

A picrotoxane-type sesquiterpene, dendroterpene E (1), together with five benzene derivatives (2-6), were isolated from the stems of Dendrobium nobile Lindl. Their structures were elucidated by spectroscopic analysis and X-ray diffraction analysis. Compound 1 was a new picrotoxane-type sesquiterpene with a C-9/C-1/O/C-11 oxetane ring, which was first encountered in this type of compounds. Compounds 1-3 exhibited inhibitory activities against α-glycosidase.

Triterpenoids and meroterpenoids with α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma australe.

Macrofungi Ganoderma is a valuable medicinal fungus resource for human health and longevity in China. In this study, ten undescribed compounds including seven lostane-type triterpenoids, ganodaustralic acids A âˆ¼ G (1-7), one pair of meroterpenoid enantiomers, (-)-6'-O-ethyllingzhiol (8) and (+)-6'-O-ethyllingzhiol (9), and one polyhydroxylated sterol, 3-O-acetyl-fomentarol C (10), together with eight known compounds (11-18), were isolated from the fruiting bodies of Ganoderma australe. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and electronic circular dichroism (ECD) calculations. Compounds 4, 8, 9, and 12 showed significant α-glucosidase inhibitory activities with IC50 values in the range of 4.1-11.7 µM, which were superior to that of positive control acarbose (213 µM). Only compound 7 exhibited weak cytotoxicity against SGC-7901 cells.

Cytotoxic Indole-Diterpenoids from the Marine-Derived Fungus Penicillium sp. KFD28.

Four new indole-diterpenoids, named penerpenes K-N (1-4), along with twelve known ones (5-16), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (4, 9, and 15) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 µM. Moreover, six compounds (5, 7, 10, 12, 14, and 15) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

Indole-Terpenoids With Anti-inflammatory Activities From Penicillium sp. HFF16 Associated With the Rhizosphere Soil of Cynanchum bungei Decne.

Four new indole-terpenoids (1-4) named encindolene A, 18-O-methyl-encindolene A, encindolene B, and encindolene C, as well as three known analogs (5-7), were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds including absolute configurations were elucidated by spectroscopic data and electronic circular dichroism (ECD) analysis. Anti-inflammatory activity evaluation revealed that compounds 1-7 inhibit the production of nitric oxide with IC50 values of 79.4, 49.7, 81.3, 40.2, 86.7, 90.1, and 54.4 µM, respectively, and decrease the levels of tumor necrosis factor-α, interleukin-6 contents in lipopolysaccharide-induced RAW264.7 macrophages.

Three New Quinazoline-Containing Indole Alkaloids From the Marine-Derived Fungus Aspergillus sp. HNMF114.

By feeding tryptophan to the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis, 3 new quinazoline-containing indole alkaloids, named aspertoryadins H-J (1-3), along with 16 known ones (4-19), were obtained. The structures of the new compounds were elucidated by the analysis of spectroscopic data combined with quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts and electron capture detector (ECD) spectra. Structurally, compound 3 represents the first example of this type of compound, bearing an amide group at C-3. Compounds 10 and 16 showed potent α-glucosidase inhibitory activity with IC50 values of 7.18 and 5.29 µM, and compounds 13 and 14 showed a clear activation effect on the ryanodine receptor from Spodoptera frugiperda (sfRyR), which reduced the [Ca2+] ER by 37.1 and 36.2%, respectively.

Nocardiopsis coralli sp. nov. a novel actinobacterium isolated from the coral Galaxea astreata.

Strain HNM0947T, representing a novel actinobacterium, was isolated from the coral Galaxea astreata collected from the coast of Wenchang, Hainan, China. The strain was found to have morphological and chemotaxonomic characteristics consistent with the genus Nocardiopsis. The organism formed abundant fragmented substrate mycelia and aerial mycelia which differentiated into non-motile, rod-shaped spores. Whole-cell hydrolysates contained meso-diaminopimelic acid and no diagnostic sugars. The major menaquinones were MK-10(H8), MK-10(H6) and MK-10(H4). The major phospholipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. The major fatty acids were iso-C16:0, anteiso-C17:0, C18:0, C18:0 10-methyl (TBSA) and anteiso-C15:0. The G+C content was 71.3 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HNM0947T belonged to the genus Nocardiopsis and shared highest sequence similarity to Nocardiopsis salina YIM 90010T (98.8%), Nocardiopsis xinjiangensis YIM 90004T(98.5%) and Nocardiopsis kunsanensis DSM 44524T (98.3%). The strain HNM0947T was distinguished from its closest type strain by low average nucleotide identity (90.8%) and dDDH values (60.4%) respectively. Based on genotypic, chemotaxonomic and phenotypic characteristics, it was concluded that strain HNM0947T represents a novel species of the genus Nocardiopsis whose name was proposed as Nocardiopsis coralli sp. nov. The type strain was HNM0947T (=CCTCC AA 2020015 T=KCTC 49525 T).

[Study on chemical constituents from fruiting bodies of Ganoderma calidophilum].

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11ß-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 µmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 µmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 µmol·L~(-1).

New Thio-Compounds and Monoterpenes With Anti-inflammatory Activities From the Fungus Aspergillus sp. CYH26.

Two new thio-compounds named aspergerthinol A and B (1 and 2) and two new monoterpenes named aspergerthinacids A and B (3 and 4) were isolated from the fungus Aspergillus sp. CYH26 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds were elucidated by spectroscopic data and quantum NMR and ECD calculations. Compounds 1 and 2 represented a new family of sulfur containing natural products with a 3-methyl-4H-cyclopenta[b]thiophen-4-one skeleton. Compounds 1-4 showed inhibitory activities against nitric oxide (NO) with IC50 values of 38.0, 19.8, 46.3, and 56.6 µM, respectively.

Metabolites From the Mangrove-Derived Fungus Cladosporium sp. HNWSW-1.

Two new benzoic acids, cladoslide A (1) and cladoslide B (2); one new ß-carboline derivative, cladospomine (3); and one new pyridin-2(1H)-one, cladoslide C (4), were isolated from the fermentation cultures of the mangrove-derived fungus Cladosporium sp. HNWSW-1, along with the previously reported N-acetyl-ß-oxotryptamine (5), (4S,5S,11R)-iso-cladospolide B (6), (4S,5S,11S)-iso-cladospolide B (7), and (4R,5S,11R)-iso-cladospolide B (8). Their structures were elucidated by spectroscopic analysis, Rh2(OCOCF3)4-induced ECD experiments, and Marfey's method. Compound 1 showed cytotoxicity against the K562 cell line with IC50 values of 13.10 ± 0.08 µM. Moreover, compounds 1 and 5 exhibited inhibitory activity against α-glycosidase with IC50 values of 0.32 ± 0.01 mM and 0.17 ± 0.01 mM, respectively.

Humulane-Type Macrocyclic Sesquiterpenoids From the Endophytic Fungus Penicillium sp. of Carica papaya.

Three new humulane-type sesquiterpenoids, penirolide A (1), penirolide B (2), and 10-acetyl-phomanoxide (3), together with three known compounds aurasperone A (4), pughiinin A (5), and cyclo(l-Leu-l-Phe) (6) were isolated from the endophytic fungus Penicillium sp. derived from the leaves of Carica papaya L. Their structures including their absolute configurations were determined based on the analysis of NMR and HRESIMS spectra, NMR chemical shifts, and ECD calculations. Compounds 2, 3, 5, and 6 significantly inhibited glucagon-induced hepatic glucose production, with EC50 values of 33.3, 36.1, 18.8, and 32.1 µM, respectively. Further study revealed that compounds 2, 3, 5, and 6 inhibited hepatic glucose production by suppression of glucagon-induced cAMP accumulation.