Yuchun Fang

Cytotoxic Alkaloids and Antibiotic Nordammarane Triterpenoids from the Marine-Derived Fungus Aspergillus sydowi

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.

Citrinin Dimers from the Halotolerant Fungus Penicillium citrinum B-57

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.

Cytotoxic Polyketides from a Marine-derived Fungus Aspergillus glaucus

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.

Gentisyl alcohol derivatives from the marine-derived fungus Penicillium terrestre.

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.

Novel open-chain cytochalsins from the marine-derived fungus Spicaria elegans.

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.

Unusual C25 steroid isomers with bicyclo[4.4.1]A/B rings from a volcano ash-derived fungus Penicillium citrinum.

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 new ergosterols from the marine-derived fungus Rhizopus sp

Six new ergosterols, including 3beta-hydroxyl-(22E, 24R)-ergosta-5,8,22-trien-7,15-dione (1), 3beta-hydroxyl-(22E, 24R)-ergosta-5,8,14,22-tetraen-7-one (2), 3beta,15beta-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-one (3), 3beta,15alpha-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-one (4), 3beta-hydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7,15-dione (5), and 5alpha,8alpha-epidioxy-23,24(R)-dimethylcholesta-6,9(11),22-trien-3beta-ol (6), have been isolated from the marine-derived fungus Rhizopus sp., along with four known ones (7-10). The structures of the new compounds were determined on the basis of extensive spectroscopic data. All compounds were evaluated for their cytotoxic activities on P388, A549, HL-60, and BEL-7420 cell lines by the MTT and SRB methods.

Carbonarones A and B, New Bioactive γ-Pyrone and α-Pyridone Derivatives from the Marine-derived Fungus Aspergillus carbonarius

Two new secondary metabolites, carbonarones A (1) and B (2), were obtained from the culture of the marine-derived fungus Aspergillus carbonarius isolated from the marine sediment collected at Weizhou island of China. Based on ESIMS, 1D and 2D NMR data, and the X-ray crystallographic analysis, their structures were elucidated as 6-benzyl-4-oxo-4H-pyran-3-carboxamide and 6-benzyl-4-hydroxy-2-oxo-1, 2-dihydropyridine-3-carbaldehyde, respectively. 1 and 2 showed moderate cytotoxicity against K562 cells with IC50 values of 56.0 and 27.8 μg/ml, respectively.

Isocoumarin derivatives from the sea squirt-derived fungus penicillium stoloniferum QY2-10 and the halotolerant fungus penicillium notatum B-52

Two isocoumarin derivatives, stoloniferol A (1) and B (2), a known 5a, 8a-epidioxy-23-methyl-(22E, 24R)-ergosta-6, 22-dien-3 β-ol (3), and a known dihydrocitrinone (4) were isolated from the ethyl acetate extract of the sea squirt-derived fungus,Penicillium stoloniferum QY2-10, and a halophilic fungus,Penicillium notatum B-52, respectively. Their structures were elucidated by spectroscopic methods and optical rotation. The stereochemistry of 2 was determined on the basis of different NOE experiments and chemical transformation. Compound 3 showed cytotoxicity against P388 cells, with an IC50 value of 4.07 μ.M.

Two New Cytotoxic Quinone Type Compounds from the Halotolerant Fungus Aspergillus variecolor

Two new quinone type compounds, variecolorquinones A (1) and B (2) together with eleven known related compounds 3∼13 have been isolated from the metabolites produced by the halotolerant fungal strain Aspergillus variecolor B-17. The structures of 1 and 2 were determined by spectroscopic methods. 1 exhibited selective cytotoxicity against A-549 cells with the IC50 values of 3.0 μM. 2 showed cytotoxicity against HL60 and P388 cells with the IC50 values of 1.3 and 3.7 μM, respectively.