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Seven new gilvocarcin-type aryl

Four new aromatic polyketides, wailupemycins M-P (1-4), and two new hydroxamate siderophores, streptamides A (5) and B (6), together with the previously reported nocardamine (7), were isolated from the marine-algae-derived Streptomyces sp. OUCMDZ-3434. Wailupemycins M-P (1-4), possessing an α-pyrone moiety, were isolated from the extract of a liquid fermentation, and the siderophores (5-7) were isolated from the extract of a solid fermentation. Their structures were assigned based on detailed spectroscopic analysis and quantum chemical calculations. Compounds 5-7 were capable of binding Fe(III). Compound 5 can form a tighter Fe(III) complex than that of deferoxamine B mesylate (DFB).

Six new sulfur-containing phenolic compounds (

Three new p-terphenyl derivatives, nocarterphenyls A-C (1-3), along with three known analogues (4-6) were isolated from the marine-derived actinobacterial strain Nocardiopsis sp. OUCMDZ-4936. Their structures were elucidated on the basis of spectroscopic analysis and a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possess a benzothiazole and benzothiazine moiety, respectively, which are rare in the skeleton of p-terphenyls. Nocarterphenyl A (1) showed potent cytotoxic activity against the HL60 and HCC1954 cancer cell lines with the IC50 values of 0.38 and 0.10 μM among 26 human cancer cell lines.

Four new aromatic polyketides, wailupemycins M-P (

Seven new ophiobolins (1–5, 12, and 14) along with the 11 known analogues (6–11, 13, 15–18) were isolated from the ethyl acetate extracts of the liquid and solid cultures of the mangrove fungus Aspergillus ustus 094102. The structures including the absolute configurations of the seven new compounds were elucidated by spectroscopic analysis, chemical methods, and quantum ECD calculations. Compounds 4–8 and 11–15 showed cytotoxicities against the G3K, MCF-7, MD-MBA-231, MCF/Adr, A549, and HL-60 human cancer cell lines with the IC50 values ranging from 0.6 to 9.5 μM.

Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC50 values of 0.32-0.96 μM. The mechanism of action studies indicated that the most effective 3-chloro-5‴-fluorofradcarbazole A (6) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G0/G1 phase. Furthermore, compound 6 can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5‴-fluorofradcarbazole A (6) is a potential candidate for developing novel anti-AML agents in the future.

Three new α-pyrones, nocapyrones E-G (1-3), and three new diketopiperazine derivatives, nocazines A-C (4-6), together with a new oxazoline compound, nocazoline A (7), were isolated from the marine-derived actinomycete Nocardiopsis dassonvillei HR10-5. The new structures of 1-7 were determined by spectroscopic analysis, X-ray single-crystal diffraction, CD spectra, and modified Mosher and Marfey methods. Compounds 1-3 showed modest antimicrobial activity against Bacillus subtilis with MIC values of 26, 14, and 12 μM, respectively.

Fractionation of the ethyl acetate extract of an acid-tolerant fungus, Penicillium purpurogenum JS03-21, resulted in the isolation of six new compounds, purpurquinones A-C (1-3), purpuresters A and B (4 and 5), and 2,6,7-trihydroxy-3-methylnaphthalene-1,4-dione (6), together with three known compounds, TAN-931 (7), (-)-mitorubrin (8), and orsellinic acid. The structures of 1-6 were elucidated primarily by NMR experiments. The absolute configurations of 1-4 were assigned on the basis of CD and NOESY data. Compounds 2-4 and 7 exhibited significant antiviral activity against H1N1, with IC50 values of 61.3, 64.0, 85.3, and 58.6 μM, respectively.

Eleven new aspochracin-type cyclic tripeptides, sclerotiotides A-K (1-11), together with three known compounds, JBIR-15 (12), aspochracin (13), and penicillic acid, were isolated from the ethyl acetate extract of the fermentation broth of the halotolerant Aspergillus sclerotiorum PT06-1 in a hypersaline nutrient-rich medium. Their structures were elucidated by spectroscopic analysis and chemical methods. Chemical transformations of 12 and 13 proved that sclerotiotides D-K (4-11) were artifacts probably formed during the fermentation or subsequent isolation steps. All 13 cyclic tripeptides have been evaluated for their antimicrobial and cytotoxic effects. Only sclerotiotides A (1), B (2), F (6), and I (9) and JBIR-15 (12) showed selective antifungal activity against Candida albicans with MIC values of 7.5, 3.8, 30, 6.7, and 30 microM, respectively.

Eight drimane sesquiterpenes (1-8), six isochromane derivatives (9-14), and three known compounds, daldinin B (15), 9alpha-hydroxy-6beta-[(2E,4E,6E)-octa-2,4,6-trienoyloxy]-5alpha-drim-7-en-11,12-olide (16), and pergillin (17), were isolated from the EtOAc extract of the marine-derived fungus Aspergillus ustus 094102. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxic effects on A549 and HL-60 cell lines were evaluated by SRB and MTT methods. Ustusorane E (13) showed significant cytotoxicity against HL-60 cells with an IC50 value of 0.13 microM. Ustusolates C (6) and E (8) exhibited moderate cytotoxicity against A549 and HL-60 cells with IC50 values of 10.5 and 9.0 microM, respectively, and ustusolate A (4) showed weak cytotoxicity against HL-60 and A549 cells with IC50 values of 20.6 and 30.0 microM, respectively.

Eight new resin glycosides, pescapreins X-XVII (1-8), were isolated from a lipophilic fraction of an ethanol extract of the entire plant of beach morning glory, Ipomoea pes-caprae. Their structures were elucidated by spectroscopic data analysis and by chemical transformation. These compounds were evaluated biologically in terms of cancer cell line cytotoxicity, antibacterial and antifungal activity, and effects on the mu-opioid receptor.

Three new diketopiperazine alkaloids, 6-methoxyspirotryprostatin B (1), 18-oxotryprostatin A (2), and 14-hydroxyterezine D (3), with an oxaspiro[4.4]lactam moiety, 14-norpseurotin A (4), and the 29-nordammarane triterpenoid 6beta,16beta-diacetoxy-25-hydroxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (5), as well as 12 known compounds (6- 17), were isolated from the ethyl acetate extract of a marine-derived fungal strain, Aspergillus sydowi PFW1-13. The structures of compounds 1- 5 were elucidated by comprehensive spectroscopic analysis. Compounds 1- 3 exhibit weak cytotoxicity against A-549 cells, with IC 50 values of 8.29, 1.28, and 7.31 microM, respectively. Compound 1 also shows slight cytotoxicity against HL-60 cells, with an IC 50 value of 9.71 microM. Compounds 4 and 5 display significant antimicrobial activities against Escherichia coli, Bacillus subtilis, and Micrococcus lysoleikticus with MICs of 3.74, 14.97, and 7.49 microM and 10.65, 5.33, and 10.65 microM, respectively.

Nine new gentisyl alcohol derivatives, namely, the trimeric terrestrol A (8), dimeric terrestrols B-H (1-7), and a monomeric derivative (12), together with four known analogues (9-11, 13) were isolated from the marine-derived fungus Penicillium terrestre. The structures of the new compounds were elucidated by spectroscopic methods including one- and two-dimensional NMR as well as low- and high-resolution mass spectrometric analysis. These new compounds (1-8, 12) showed cytotoxic effects on HL-60, MOLT-4, BEL-7402, and A-549 cell lines with IC50 values in the range 5-65 microM. Compound 6 also showed moderate inhibitory activity against protein tyrosine kinases (Src and KDR). Furthermore, all new compounds exhibited moderate radical scavenging activity against DPPH with IC50 values in the range 2.6-8.5 microM.

Twelve new compounds, variecolorins A-L ( 1- 12), together with eleven known analogues ( 13- 23) were isolated from the broth of a halotolerant fungus, Aspergillus variecolor. The structures of compounds 1- 12 were determined by chemical and spectroscopic methods. Compounds 1- 11, 13- 15, and 20- 23 exhibited weak radical scavenging activity against DPPH, with IC 50 values from 43 to 103 microM. The new compounds 1- 12 all were essentially nontoxic against the P388, HL-60, BEL-7402, and A-549 cell lines with IC 50 values from 70 to 260 microM.

Three new thiodiketopiperazines, named phomazines A-C (1-3), along with 10 known analogues (4-13), were isolated from the fermentation broth of an endophytic fungus, Phoma sp. OUCMDZ-1847, associated with the mangrove plant Kandelia candel. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic, X-ray crystallographic, and Mosher's methods along with quantum ECD and (13)C NMR calculations. Compounds 2, 4, 5, 11, and 12 showed cytotoxicities against the HL-60, HCT-116, K562, MGC-803, and A549 cell lines with IC50 values in the range 0.05 to 8.5 μM.

Three new sulfated alkenes (1-3), trimethylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, dimethylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, and 2'-methyl-4'-oxobutan-2-ylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1-sulfate, were isolated from an echinoderm, Temnopleurus hardwickii. Their structures were elucidated by spectral analysis and chemical degradation methods.

An aciduric fungal strain, Penicillium camemberti OUCMDZ-1492, was isolated from an acidic marine niche, mangrove soil and mud, around the roots of Rhizophora apiculata. Six new indole-diterpenoids (1-6), along with five known analogues, emindole SB (7), 21-isopentenylpaxilline (8), paspaline (9), paxilline (10), and dehydroxypaxilline (11), were isolated from the fermentation broth of P. camemberti OUCMDZ-1492 grown at pH 5.0. On the basis of spectroscopic analyses, CD spectra, quantum ECD calculations, and chemical methods, new structures 1-6 were established as 3-deoxo-4b-deoxypaxilline, 4a-demethylpaspaline-4a-carboxylic acid, 4a-demethylpaspaline-3,4,4a-triol, 2'-hydroxypaxilline, 9,10-diisopentenylpaxilline, and (6S,7R,10E,14E)-16-(1H-indol-3-yl)-2,6,10,14-tetramethylhexadeca-2,10,14-triene-6,7-diol, respectively. Compounds 1-3 and 5-10 exhibited significant activity against the H1N1 virus with IC50 values of 28.3, 38.9, 32.2, 73.3, 34.1, 26.2, 6.6, 77.9, and 17.7 μM, respectively. The results showed that 3-oxo, 4b-hydroxy, and 9-isopentenyl substitutions tend to increase the anti-H1N1 activity of hexacyclic indole-diterpenoids.

Five new bipyridine alkaloids (1–5) and a new phenylpyridine alkaloid (6), which we name caerulomycins F–K, along with five known analogues (7–11), were isolated from the marine-derived actinomycete Actinoalloteichus cyanogriseus WH1-2216-6. The structures of 1–6 were established on the basis of spectroscopic analyses and chemical methods. Compounds 1–10 showed cytotoxicity against the HL-60, K562, KB, and A549 cell lines, with IC50 values of 0.26 to 15.7 μM. Compounds 7 and 8 also showed antimicrobial activities against Escherichia coli, Aerobacter aerogenes, Pseudomonas aeruginosa, and Candida albicans, with MIC values of 9.7 to 38.6 μM.

Five new cerebrosides, chrysogesides A-E (1-5), and two new 2-pyridone alkaloids, chrysogedones A and B (6 and 7), were isolated from the fermentation broth of Penicillium chrysogenum PXP-55, a halotolerant fungus grown in a hypersaline medium. Among them, chrysogesides B-D (2-4) are the first cerebrosides that contain an unsaturated C(19)-fatty acid. Their structures were identified by spectroscopic and chemical methods, including CD spectroscopy as well as the modified Mosher's method. Compound 2 showed antimicrobial activity against Enterobacter aerogenes with an MIC value of 1.72 μM.

Two new polyphenols containing both phenolic bisabolane sesquiterpenoid and diphenyl ether units, expansols A (1) and B (2), and two new phenolic bisabolane sesquiterpenoids, (S)-(+)-11-dehydrosydonic acid (3) and (7S,11S)-(+)-12-acetoxysydonic acid (4), along with two known compounds, (S)-(+)-sydonic acid (5) and diorcinol (6), were isolated from the metabolites of the marine-derived fungus Penicillium expansum 091006 endogenous with the mangrove plant Excoecaria agallocha. On the basis of spectroscopic analysis, chemical transformation, and theoretical calculation, the structures of 1-4 were elucidated as (S)-(+)-2-[3-hydroxy-4-(2- methoxy-6-methylheptan-2-yl)benzyl]-5-(3-hydroxy-5-methylphenoxy)-3-methylphenol, S-(+)-2-[3-hydroxy-4-(2-hydroxy-6-methylheptan-2-yl)benzyl]-5-(3-hydroxy-5-methylphenoxy)-3-methylphenol, (S)-(+)-3-hydroxy-4-(2-hydroxy-6-methylhept-6-en-2-yl)benzoic acid, and 4-[(2S,6S)-7-acetoxy-2-hydroxy-6-methylheptan-2-yl]-3-hydroxybenzoic acid, respectively. Expansol A (1) exhibited moderate cytotoxicity against the HL-60 cell line with an IC(50) value of 15.7 microM, and expansol B (2) inhibited the proliferation of A549 and HL-60 cells with IC(50) values of 1.9 and 5.4 microM, respectively.

In order to search for structurally novel and bioactive natural compounds from marine-derived fungi, a halotolerant fungal strain (THW-18) identified as Alternaria raphani was isolated from sediment collected in the Hongdao sea salt field. From the ethyl acetate extract of Alternaria raphani, three new cerebrosides, alternarosides A-C (1-3), and a new diketopiperazine alkaloid, alternarosin A (4), together with 15 known compounds were isolated and identified by spectroscopic and chemical methods, as well as X-ray crystal diffraction analysis. Compounds 1-4 showed weak antibacterial activity against Escherichia coli, Bacillus subtilis, and Candida albicans with MIC values ranging from 70 to 400 muM.

Eight new aromatic polyketides (2, 4-6, 8, 14, 16, and 17) together with eight known analogues (3, 7, 9-13, and 15) were isolated from the marine-derived fungus Aspergillus glaucus. The structures and stereochemistry of the new compounds were elucidated by spectroscopic and chemical methods, and their cytotoxicities were evaluated against the HL-60 and A-549 cell lines.

Eleven new unusual C25 steroid isomers with bicyclo[4.4.1]A/B rings, 24- epi-cyclocitrinol (1), 20-O-methyl-24-epi-cyclocitrinol (3), 20-O-methylcyclocitrinol (4), 24-oxocyclocitrinol (7), 12 R-hydroxycyclocitrinol (8), neocyclocitrinols B (10) and D (12), erythro-23-O-methylneocyclocitrinol (13), threo-23-O-methylneocyclocitrinol (14), isocyclocitrinol B (15), and precyclocitrinol B (18), and five known steroids, cyclocitrinol (2), neocyclocitrinols A (9) and C (11), isocyclocitrinol A (16), and 22-O-acetylisocyclocitrinol A (17), were characterized from cultures of the volcanic ash-derived fungus Penicillium citrinum HGY1-5. Their structures and absolute configurations were established by spectroscopic and chemical methods together with X-ray diffraction analysis. Compounds 3, 4, and 10- 14 were determined to be artifacts on the basis of acidic transformation of 1- 4. The biosynthetic origin of these steroids derived from ergosterol was investigated by feeding (13)C-labeled acetates to the growing cultures of P. citrinum HGY1-5. The biological activities of all 16 steroids were tested using the cAMP assay on GPR12-CHO and WT-CHO cells. The results showed that compounds 1, 2, 10, 11, and 14 could induce the production of cAMP in GPR12-transfected CHO cells.

Six novel open-chain cytochalasins (1−6) and one known [12]-cytochalasin (7) have been isolated from the fermentation broth of a marine-derived fungus, Spicaria elegans. Cytochalasins Z10−Z15 (1−6) are the first reported cytochalasins that contain an open chain to date. The structures of these new compounds were elucidated by spectroscopic methods. The cytotoxic effects on P388, A-549, HL-60, and BEL-7402 cell lines of all compounds were evaluated by the MTT method.

In order to search for structurally novel and bioactive natural compounds from microorganisms, a halotolerant fungal strain, Penicillium citrinum B-57, which mainly produces citrinin derivatives, was isolated from sediments collected from the Jilantai salt field. From the ethyl acetate extract of P. citrinum B-57, two new citrinin dimers, pennicitrinone C ( 1) and penicitrinol B ( 2), and 11 known related compounds were isolated and identified by spectroscopic and chemical methods. These compounds showed antioxidative activity against DPPH radicals with IC 50 values ranging from 0.8 to 59 microM.

Three new quinazoline alkaloids, aurantiomides A (1), B (2), and C (3), along with the known metabolite anacine (4) were isolated from the sponge-derived fungus strain Penicillium aurantiogriseum SP0-19 by bioassay-guided fractionation. Their structures were elucidated by spectroscopic and chemical methods. Their absolute configurations were deduced by comparison of their Cotton effects with anacine (4) and by chemical transformations. Compounds 2 and 3 showed moderate cytotoxicities against HL-60, P388 and BEL-7402, P388 cell lines, respectively.

The three new 10-phenyl-[12]-cytochalasins Z7, Z8, and Z9 (1−3), together with two known analogues, cytochalasins E (4) and K (5), were isolated from the marine-derived fungus Spicaria elegans. This is only the second report to date that cytochalasins contain a 12-membered macrocyclic ring. The structures of the three new cytochalasins were elucidated by spectroscopic methods, and their absolute configurations were determined for the first time by the modified Mosher's method. All five cytochalasins were evaluated for their cytotoxic effects on P388 and A-549 cell lines by the MTT method.

Two new triterpenoid saponin dimers, rubupungenosides A (1) and B (2), were isolated in their methylated forms 1a and 2a, respectively, from an ethanol extract of the aerial parts of Rubus pungens. The structures of 1a and 2a were established on the basis of spectroscopic and chemical methods.