You-Min Ying

Ceriponols A-K, tremulane sesquitepenes from Ceriporia lacerate HS-ZJUT-C13A, a fungal endophyte of Huperzia serrata.

Tremulane sesquiterpenes ceriponols A-K, together with three known ones tremulenediol A, 11,12-dihydroxy-1-tremulen-5-one and conocenol B, were isolated from the cultures of Ceriporia lacerate, a fungal endophyte residing in the stems of the medicinal plant Huperzia serrata. Among these isolates, ceriponol B possessed an unprecedent 12-nortremulane skeleton. The structures of all isolates were elucidated by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. The cytotoxic activities of ceriponols A-K were evaluated against three human tumor cell lines (HeLa, HepG2, and SGC 7901). Ceriponols F and K exhibited moderate cytotoxicity against all the tested human cancer cell lines with IC50 values ranging from 32.3 ± 0.4 to 173.2 ± 1.5 μM, while ceriponol G showed slightly better cytotoxicity against a HeLa cell line.

Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus

Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus.

Bioactive metabolites from Penicillium sp. P-1, a fungal endophyte in Huperzia serrata

A chemical study of metabolites of the strain Penicillium sp. P-1, an endophyte from the stems of Huperzia serrata, furnished a new chromone derivative, (2S)-2,3-dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-1-enyl]- chroman-4-one (1), an enantiomer of a known compound, and seven known compounds 2–8. The structure and absolute configuration of 1 were established using spectroscopic methods, including extensive 2D NMR and CD analyses. Cytotoxic activity of compounds 1–3 against HeLa and HepG2 cell lines were evaluated, in which compounds 2 and 3 exhibited marked cytotoxic activity against HeLa cells.

Indole-benzodiazepine-2,5-dione derivatives from Neosartorya fischeri

One new aszonalenin analogue, 6-hydroxyaszonalenin was isolated from the culture of Neosartorya fischeri CGMCC 3.5378, together with aszonalenin, acetylaszonalenin, fumitremorgin B, verruculogen, and aszonapyrones A and B. The structure of the new metabolite was elucidated by comprehensive spectroscopic analyses, especially HR-ESI-MS and NMR experiments. The absolute configuration of 6-hydroxyaszonalenin was determined by X-ray diffraction. To the best of our knowledge, aszonapyrone B was reported for the first time from this species.

Alkaloids and Nucleoside Derivatives from a Fungal Endophyte of Huperzia serrata

Endophytes are microorganisms growing in the tissues of their host plants without causing apparent disease symptoms [1]. The host plants offer the endophytes a unique biotope, the growth in which involves continual metabolic interactions with the hosts. Such interactions may enhance the synthesis of secondary metabolites [2]. Hence, endophytes represent an untapped source of bioactive secondary metabolites. In our previous investigation on fungal endophytes from Huperzia serrata, one strain, Penicillium sp. HS-3 (code name for this strain), was isolated from the stems of the plant and furnished four diketopiperazine alkaloids in liquid potato-dextrose medium [3]. Subsequent study indicated that this fungus can also produce alkaloids in liquid Sabouraud s medium. To investigate the metabolites of this fungus in liquid Sabouraud s medium, scaledup fermentation was carried out. The fungus was cultivated in 500 mL Erlenmeyer flasks each containing 300 mL liquid Sabouraud s medium (peptone 10 g; glucose 40 g for 1 L) to a total of 60 L at 28 C. The flasks were first incubated on rotary shakers for 6 days at 185 rpm, and then cultivated for another 20 days without agitation. The culture was filtered through cheesecloth. The broth was condensed to a volume of 4 L and then adjusted with 0.5 M HCl to pH 4. The acidic mixture was extracted with EtOAc (6 4 L), and the organic phase was condensed under reduced pressure to give a nonalkaloid residue (47.7 g). The aqueous phase was brought to pH 10 by addition of 1 M Na2CO3 and partitioned with chloroform (6 0.5 L) to give the crude alkaloids (4.3 g), which were then subjected to column chromatography (CC) on MCI-CHP20P gel eluted with MeOH–H2O (2:3 9:1) to afford three major fractions A–C. Fraction A was applied to silica gel CC (SiO2, CHCl3–MeOH 20:1) to yield 1 (24.3 mg). Fraction B was separated by CC (SiO2, CHCl3–MeOH 15:1) to give 2 (2.8 mg). Fraction C was also purified by CC (RP-18, MeOH–H2O 4:6) to afford 3 (8.7 mg). The nonalkaloid residue was first subjected to CC (SiO2, CHCl3–MeOH 20:1 10:1) to offer four fractions D–G. Fraction E (2.7 g) was then subjected to CC (MCI-CHP20P gel, MeOH–H2O 2:3 9:1) to give two subfractions E1 and E2, which were further purified by CC (HW-40C, MeOH) to furnish 4 (23 mg) and 6 (4 mg), respectively. Fraction F (4.3 g) was also separated by CC (MCI-CHP20P gel, MeOH–H2O 0:10 1:3) to give two subfractions F1 and F2, both of which were subjected to CC (RP-18, MeOH–H2O 1:9) as the final step of purification to give 7 (6.7 mg) and 5 (17.4 mg), respectively. The structures of the isolates were elucidated on the basis of detailed analysis of their spectroscopic data, including NMR and MS spectra. They were identified as perlolyrine (1), harmane (2), norharmane (3), cyclo(D-Pro-L-Trp) (4), thymidine (5), 5 -O-acetylthymidine (6), and 5 -O-acetyluridine (7). NMR signal assignments of compounds 1–7 were made by elucidating the two-dimensional NMR spectra and by comparing the data with those in the literatures.

Antiproliferative Prenylated Xanthones from the Pericarps of Garcinia mangostana

Xanthones are a kind of natural products bearing a unique tricyclic aromatic system (C6–C3–C6) [1]. The structural diversities of these compounds arise mainly from the different substitutions of the A and B rings in the skeleton, with isoprene, methoxyl, and hydroxyl groups, being the most frequently occurring substituents. Accordingly, xanthones can be classied into several groups including simple oxygenated xanthones, prenylated xanthones, xanthone glycosides, and xanthonolignoids based on these substituents [2]. In recent years, xanthones have been identified as promising bioactive compounds with wide ranging and potentially usefull biological activities such as anticancer, anti-HIV, anti-inflammatory, antibacterial, and neurotrophic activities [3]. Garcinia mangostana is a tropical fruit native to Southeast Asia that has long been noted for its medicinal and health promoting properties [4]. Compared to the other species in the genus Garcinia, G. mangostana has captured the most attention due to its fruit, which was always referred to as the “queen of fruits.” The pericarps of G. mangostana fruit, a traditional medicine used for the treatment of infection, wounds, inflammation, and diarrhea in Southeast Asia, have recently been noted to be an abundant source of xanthones [1]. Herein, as part of our ongoing programs on the exploration of bioactive xanthones from Garcinia [5] and other related genus [6], eight prenylated xanthones were identified from the pericarps of G. mangostana and subjected to antiproliferative assay. G. mangostana fruits were purchased from the fruit market in Hangzhou and identified by Prof. Fa-Song Wang (Hubei University for Nationalities, P. R. China). A voucher specimen (No. ZJUTGM201009) was deposited with the Zhejiang University of Technology. The air-dried pericarps of G. mangostana fruits (4.5 kg) were crushed and extracted with ethanol (3 30 L). The extracts, after vacuum evaporation, was suspended in 2 L of distilled water and partitioned successively with petroleum ether (4 4 L) and CHCl3 (4 4 L) to give the petroleum ether-soluble and the CHCl3-soluble residues, respectively. The CHCl3-soluble residue (425 g) was subjected to column chromatography (CC) on silica gel eluting with petroleum ether– EtOAc (10:1 0:1) to furnish three fractions A–C. Fraction A was seprated by CC (MCI-CHP20P, CH3OH–H2O, 5:5 10:0) to afford two subfractions A1 and A2. Subfraction A1 (175.8 mg) was further purified by CC (HW-40, CH3OH) to give 2 (46.7 mg). Subfraction A2 (330.4 mg) was purified on CC (silica gel, petroleum ether–EtOAc, 15:1 10:1) to give 1 (16.2 mg), 5 (7.1 mg), and 8 (3 mg). Fraction B (2 g) was first separated by CC (silica gel, petroleum ether–acetone, 6:1) to give two subfractions B1 and B2, which were purified by CC (HW-40, CH3OH) to furnish 3 (25.7 mg) and 4 (30.0 mg), respectively. Fraction C was first recrystallized and filtered to produce 7 (ca. 100 g), and the filtrate was subjected to CC (silica gel, petroleum ether–acetone, 6:1) followed by CC (HW-40, CH3OH) to afford 6 (17.9 mg). The compounds were identified as 7-O-methylgarcinone E (1) [7], 8-desoxygartanin (2) [8], gartanin (3) [8], garcinone E (4) [9], 4 ,5 -dihydro-1,3,6-trihydroxy-6 ,6 -dimethyl-2,5-bis(3-methylbut-2-en-1-yl)pyrano[2 ,3 :7,8]xanthone (5) [10], 9-hydroxycalabaxanthone (6) [8, 11], -mangostin (7) [12], and tovophyllin A (8) [13] by spectroscopic methods, including NMR and mass spetrometry. These compounds have been previously isolated from the G. mangostana, but this is the first report of their co-occurrence at the same time in the plants.

Bergamotane Sesquiterpenes with Alpha-Glucosidase Inhibitory Activity from the Plant Pathogenic Fungus Penicillium expansum.

Two new bergamotane sesquiterpene lactones, named expansolides C and D (1 and 2), together with two known compounds expansolides A and B (3 and 4), were isolated from the plant pathogenic fungus Penicillium expansum ACCC37275. The structures of the new compounds were established by detailed analyses of the spectroscopic data, especially 1D‐, 2D‐NMR, and HR‐ESI‐MS. In an in vitro bioassay, the epimeric mixture of expansolides C and D (1 and 2) (in a ratio of 2:1 at the temprature of the bioassay) exhibited more potent α‐glucosidase inhibitory activity (IC50 =0.50 ± 0.02 mm) as compared with the positive control acarbose (IC50 = 1.90 ± 0.05 mm). To the best of our knowledge, it was the first report on the α‐glucosidase inhibitory activity of bergamotane sesquiterpenes.

A New Rumenic Acid Derivative from the Roots of Cudrania tricuspidata

A new rumenic acid derivative, threo-9,10-O-isopropylidene-13-hydroxy-(11E)-octadecenoic acid (1), and two known compounds, steppogenin (2) and oxyresveratrol (3), were isolated from the roots of Cudrania tricuspidata. The structure of the new compound was established by spectroscopic methods. All the compounds were evaluated for their cytotoxicity against three human tumor cell lines (HepG2, HCT-116, and SGC-7901). Unfortunately, none of them exhibited significant cytotoxicity at a concentration of 100 μM.

Lupane‐ and Friedelane‐Type Triterpenoids from Celastrus stylosus

Two new triterpenoids, 30‐hydroxylup‐20(29)‐ene 3β‐caffeate (1) and 24‐nor‐friedelan‐6α,10‐dihydroxy‐1,2‐dioxo‐4,7‐dien‐29‐oic acid (2), together with eight known compounds 3–10, were isolated from the roots of Celastrus stylosus. The structures of these compounds were elucidated on the basis of spectroscopic analyses. To the best of our knowledge, this represents the first study on the chemical constituents of C. stylosus. The antiproliferative activities of the triterpenoids against six human cancer cell lines (PANC‐1, A549, PC‐3, HepG2, SGC‐7901, and HCCLM3) were evaluated. Compounds 3, 4, and 10 exhibited comparable activities against PC‐3 and HCCLM3 cell lines as the positive control taxol.

Neofipiperzine D, a new prenylated indole alkaloid metabolite of the fungus Neosartorya fischeri

A new prenylated indole alkaloid, neofipiperzine D, was isolated from the cultures of Neosartorya fischeri, together with three known metabolites fumitremorgin C, ergosterol, and ergosterol peroxide. The structure of the new compound was established by detailed analysis of its spectroscopic data, especially 1D, 2D NMR and HR-ESI-MS data. In an in vitro assay, neofipiperzine D did not exhibit any significant cytotoxicity against MCF-7, H1299, HUVEC, and MDA-MB-231 cell lines at a concentration of 20 μM.