Curvularin derivatives from the marine mangrove derived fungus Penicillium sumatrense MA-325.

Sumalarins D-G (1-4), four previously undescribed curvularin derivatives, along with two known related metabolites, curvularin (5) and dehydrocurvularin (6), were isolated and identified from the mangrove-derived fungus Penicillium sumatrense MA-325. Among them, sumalarin D (1) represents a unique example of curvularin derivative featuring a 5-methylfuran-2-yl-methyl group. Their structures were elucidated based on analysis of NMR and MS data as well as comparison of ECD spectra and quantum chemical calculations of NMR, and compound 1 was confirmed by X-ray crystallographic analysis. Compounds 1, 2, 5, and 6 are active against aquatic pathogenic bacteria Vibrio alginolyticus and V. harveyi with MIC values ranging from 4 to 64 µg/mL, while compound 6 is cytotoxic against tumor cell lines 5673, HCT 116, 786-O, and Hela with IC50 values of 3.5, 10.6, 10.9, and 14.9 µM, respectively.

Isolation and characterization of three pairs of verrucosidin epimers from the marine sediment-derived fungus Penicillium cyclopium and configuration revision of penicyrone A and related analogues.

Verrucosidins, a methylated α-pyrone class of polyketides rarely reported upon, have been implicated in one or more neurological diseases. Despite the significance of verrucosidins as neurotoxins, the absolute configurations of most of the derivatives have not been accurately characterized yet. In this study, three pairs of C-9 epimeric verrucosidin derivatives, including the known compounds penicyrones A and B (1a/1b) and 9-O-methylpenicyrones A and B (2a/2b), the new compounds 9-O-ethylpenicyrones A and B (3a/3b), together with the related known derivative verrucosidin (4), were isolated and identified from the culture extract of Penicillium cyclopium SD-413, which was obtained from the marine sediment collected from the East China sea. Their structures were established based on an in-depth analysis of nuclear magnetic resonances (NMR) and mass spectroscopic data. Determination of the absolute configurations of these compounds was accomplished by Mosher's method and time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) and optical rotation (OR). The configurational assignment of penicyrone A demonstrated that the previously reported C-6 absolute configuration of verrucosidin derivatives needs to be revised from (6S) to (6R). The 9R/9S epimers of compounds 1-3 were found to exhibit growth inhibition against some pathogenic bacteria, indicating that they have potential as lead compounds for the creation of antimicrobial agents. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00173-2.

Oxepine-containing pyrazinopyrimidine alkaloids and quinolinone derivatives produced by Aspergillus versicolor AS-212, a deep-sea-derived endozoic fungus.

Four new oxepine-containing pyrazinopyrimidine alkaloids, versicoxepines A - D (1-4), two quinolinone alkaloid analogs including 3-hydroxy-6-methoxy-4-phenylquinolin-2(1H)-one (5) and 3-methoxy-6-hydroxy-4-phenylquinolin-2(1H)-one (6) which were new naturally occurring compounds, together with two known compounds (7 and 8) were isolated from Aspergillus versicolor AS-212, an endozoic fungus isolated from the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive analysis of the spectroscopic and X-ray crystallographic data as well as by chiral HPLC analysis, ECD calculation, and DP4+ probability prediction. Structurally, versicoxepines B and C (2 and 3) represent the first example of a new oxepine-containing pyrazinopyrimidine alkaloid whose cyclic dipeptide moiety is composed of the same type of amino acid (Val or Ile). Compound 5 displayed antibacterial activity against aquatic pathogens, Vibrio harveyi and V. alginolyticus, with MICs of 8 µg/mL.

Diketopiperazine Alkaloids and Bisabolene Sesquiterpenoids from Aspergillus versicolor AS-212, an Endozoic Fungus Associated with Deep-Sea Coral of Magellan Seamounts.

Two new quinazolinone diketopiperazine alkaloids, including versicomide E (2) and cottoquinazoline H (4), together with ten known compounds (1, 3, and 5-12) were isolated and identified from Aspergillus versicolor AS-212, an endozoic fungus associated with the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts. Their chemical structures were determined by an extensive interpretation of the spectroscopic and X-ray crystallographic data as well as specific rotation calculation, ECD calculation, and comparison of their ECD spectra. The absolute configurations of (-)-isoversicomide A (1) and cottoquinazoline A (3) were not assigned in the literature reports and were solved in the present work by single-crystal X-ray diffraction analysis. In the antibacterial assays, compound 3 exhibited antibacterial activity against aquatic pathogenic bacteria Aeromonas hydrophilia with an MIC value of 18.6 µM, while compounds 4 and 8 exhibited inhibitory effects against Vibrio harveyi and V. parahaemolyticus with MIC values ranging from 9.0 to 18.1 µM.

Isolation and Characterization of Antibacterial Carotane Sesquiterpenes from Artemisia argyi Associated Endophytic Trichoderma virens QA-8.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M (1-5), which have diverse substitution patterns, and seven known related analogues (6-12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1-3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7ß-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Antibacterial Alkaloids and Polyketide Derivatives from the Deep Sea-Derived Fungus Penicillium cyclopium SD-413.

Nine secondary metabolites (1-9), including two new polyketide derivatives 9-dehydroxysargassopenilline A (4) and 1,2-didehydropeaurantiogriseol E (5), along with seven known related secondary metabolites (1-3 and 6-9), were isolated and identified from the deep sea-derived fungus Penicillium cyclopium SD-413. Their structures were elucidated on the basis of 1D/2D NMR spectroscopic and mass spectrometric analysis and the absolute configurations were determined by the combination of NOESY correlations and time-dependent density functional (TDDFT) ECD calculations. Compounds 1-9 inhibited some pathogenic bacteria including Escherichia coli, E. ictaluri, Edwardsiella tarda, Micrococcus luteus, Vibrio anguillarum, and V. harveyi, with MIC (minimum inhibitory concentration) values ranging from 4 to 32 µg/mL.

Polyketides and Terpenoids with Potent Antibacterial Activities from the Artemisia argyi-Derived Fungus Trichoderma koningiopsis QA-3.

The AcOEt extract of Artemisia argyi-derived fungus Trichoderma koningiopsis QA-3 showed potent inhibitory activity against pathogenic bacteria. Fractionation of the extract resulted in the isolation of three new polyketides (1-3) and two new terpenoids (4 and 5), together with three known metabolites (6-8). Their chemical structures were analyzed by NMR spectra, ECD, HR-ESI-MS or HR-EI-MS, optical rotation, and X-ray crystallographic data, as well as by comparison with literature reports. In the antibacterial assays, 3-hydroxyharziandione (4) showed potent activity against human pathogen Escherichia coli with an MIC value of 0.5 µg/mL, while 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one exhibited strong activity against marine-derived aquatic pathogen Micrococcus luteus with an MIC value of 1.0 µg/mL.

Cadinane and carotane derivatives from the marine algicolous fungus Trichoderma virens RR-dl-6-8.

Eight cadinane derivatives, trichocadinins H - N (1-7) and methylhydroheptelidate (8), and two carotane derivatives, 14-O-methyltrichocarotin G (9) and 14-O-methyl CAF-603 (10), including eight new ones (1-6, 9, and 10), were isolated from the culture of Trichoderma virens RR-dl-6-8 obtained from the organohalogen-enriched marine red alga Rhodomela confervoides. Their structures and relative configurations were established by analysis of NMR and mass spectroscopic data, and the absolute configurations were assigned on the basis of ECD curves, highlighted by the ECD diversity of carboxylic acid derivatives. Among the isolates, 1 with a halogen atom and 8, a new naturally occurring compound, are 2,3-seco-cadinane sesquiterpenes, and the epimeric 2 and 3 feature a 2-nor-cadinane skeleton. A commercially-sourced compound with the same planar structure as that of 7 has been reported in a patent, but its configuration was not given. Compounds 1-10 exhibited growth inhibition of some marine phytoplankton species.

Highly oxygenated polyketides produced by Trichoderma koningiopsis QA-3, an endophytic fungus obtained from the fresh roots of the medicinal plant Artemisia argyi.

Eight new highly oxygenated fungal polyketides, namely, 15-hydroxy-1,4,5,6-tetra-epi-koninginin G (1), 14-hydroxykoninginin E (2), koninginin U (3), 4'-hydroxykoninginin U (4), koninginin V (5), 14-ketokoninginin B (6), 14-hydroxykoninginin B (7), and 7-O-methylkoninginin B (8), together with six known related analogues (9-14), were isolated from Trichoderma koningiopsis QA-3, a fungus obtained from the inner root tissue of the well known medicinal plant Artemisia argyi. All these compounds are bicyclic polyketides, with compound 1 contains unusual hemiketal moiety at C-5 and compounds 2-14 having ketone group at C-1 and double bond at C-5(6). The structures and absolute configurations of the new compounds were established by spectroscopic analysis, X-ray crystal diffraction, modified Mosher's method, and ECD calculation. The absolute configurations of the known compounds 9, 10, and 12 were determined by X-ray crystal diffractions for the first time. The antimicrobial activities against human pathogen, marine-derived aquatic bacteria, and plant-pathogenic fungi of compounds 1-14 were evaluated, and compound 1 showed remarkable activity against aquatic pathogen Vibrio alginolyticus with MIC value 1 µg/mL, which is as active as that of the positive control.

Trichocadinins B-G: Antimicrobial Cadinane Sesquiterpenes from Trichoderma virens QA-8, an Endophytic Fungus Obtained from the Medicinal Plant Artemisia argyi.

Trichocadinins B-G (1-6), six new cadinane-type sesquiterpene derivatives, each with C-14 carboxyl functionality, were isolated from the culture extract of Trichoderma virens QA-8, an endophytic fungus obtained from the fresh inner tissue of the medicinal plant Artemisia argyi. Their structures were elucidated by interpretation of the NMR spectroscopic and mass spectrometric data. The structures and absolute configurations of compounds 1 and 3 were confirmed by X-ray crystallographic analysis. Compounds 1-3 showed antibacterial and antifungal activity.