Xue-Qiong Yang

A new cyclic tetrapeptide from an endophytic Streptomyces sp. YIM67005.

One new cyclic tetrapeptide, cyclo(l-Tyr-l-Pro-l-Phe-trans-4-hydroxy-l-Pro) (1), together with two known cyclodipeptides, cyclo(l-Phe-trans-4-hydroxy-l-Pro) (2) and cyclo(l-Val-l-Tyr) (3), were isolated from the fermentation broth of Streptomyces sp. YIM67005 associated with Inula cappa DC. The planar structure of compound 1 was determined on the basis of spectroscopic techniques, while the absolute configurations of the amino acid residues were determined by the application of the advanced Marfey method. The cytotoxicity and antimicrobial activity of compound 1 were investigated.

Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086

A new benzamide (1) and four known compounds (2–5) were isolated from endophytic Streptomyces YIM67086, and their structures were determined as 2-amino-3,4-dihydroxy-5-methoxybenzamide (1), 4-hydroxy-3-methoxybenzoic acid (2), phenylacetic acid (3), N-acetyltyramine (4) and p-hydroxytruxinic acid (5). Compound 5 was first found in the microorganism. The antimicrobial activities of compounds 1–5 and antioxidant activity of compound 1 were investigated.

Anti-phytopathogen, multi-target acetylcholinesterase inhibitory and antioxidant activities of metabolites from endophytic Chaetomium globosum

Abstract Fourteen metabolites with various structure types were isolated from endophytic Chaetomium globosum. Five compounds were separated from genus Chaetomium for the first time. Some compounds exhibited remarkable inhibition against phytopathogenic fungi causing root rot of Panax notoginseng. Compounds 1–5 had significant DPPH-free radical-scavenging activity. Compounds 3 and 5 indicated significant inhibitions against the acetylcholinesterase (AChE). From preliminary structure–activity relationship, it was found that the oxygenic five-membered ring of 3 and 5 was crucial in the anti-AChE activity. These structures provide new templates for the potential treatment and management of plant diseases and Alzheimer disease.

A new natural nucleotide and other antibacterial metabolites from an endophytic Nocardia sp.

Nine compounds were isolated from Nocardia sp. YIM 64630, and their structures were elucidated as 5′-O-acetyl-2′-deoxyuridine (1), 22E,24R-5α,6α-epoxyergosta-8(14),22-diene-3β,7α-diol (2), 22E,24R-5α,6α-epoxyergosta-8,22-diene-3β,7α-diol (3), 22E,24R-ergosta-7,22-diene-3β,5α,6β-triol (4), 5α,8α-epidioxyergosta-6,22-dien-3β-ol (5), 4′,5,6-trihydroxy-7-methoxyisoflavone (6), 2,4,4′-trihydroxy-deoxybenzoin (7), methyl [4-hydroxyphenyl]acetate (8) and daidzein by extensive spectroscopic analyses. Compound 1 was isolated from natural resources for the first time. The antimicrobial and antioxidant activities of compounds 1–8 were investigated.

A new daidzein derivative from endophytic Streptomyces sp. YIM 65408

A new daidzein derivative, 1″-O-methyl-8-hydroxymethyl-daidzein (1) was isolated from Streptomyces sp. YIM 65408 in soybean powder containing medium. The structure was elucidated on the basis of extensive 1D and 2D NMR as well as HR-ESI-MS spectroscopic analyses. The radical-scavenging activity and cytotoxicity of compound 1 were also investigated, and 1 was found to be more active than daidzein in the 2,2-diphenyl-1-picrylhydrazyl method with IC50 at 0.60 mmol/L, but no cytotoxicity of 1 against HL-60, SMMC-7721, A-549, MCF-7 and SW480 cell lines was shown. The possible biosynthesis pathway from daidzein (2) to compound 1 was proposed.

Cyclodipeptides from the Secondary Metabolites of Two Novel Actinomycetes

Abstract Aim To investigate the secondary metabolites of two novel actinomycetes in order to find new compounds or effective components. Methods Compounds were isolated on silica gel column. The structures were elucidated on the basis of spectral data. Results Four cyclodipeptides were isolated from the fermentation broth of Sphaerisporangium album, and their structures were determined as cyclo (L-Pro-L-Asn) ( 1 ), cyclo (L-Pro-L-Ser) ( 2 ), cyclo (L-Pro-L-Ala) ( 3 ), and cyclo (L-Pro-L-Thr) ( 4 ). Three cyclodipeptides were isolated from the fermentation broth of Kribbella yunnanensis, and their structures were determined as cyclo (L-Pro-L-Ser) ( 2 ), cyclo (L-Pro-L-Thr) ( 4 ), and cyclo-di- N δ -acetyl-L-ornithyl ( 5 ). Conclusion 5 was a new natural compound. The full assignments of 1 H and 13 C NMR chemical shifts for 1 and 5 were obtained by 2D NMR firstly. All compounds were isolated from these two actinomycetes for the first time. When tested against tumor cell line panel (k563), 1 displayed cytotoxicity.

Novel Isochroman Dimers from Stachybotrys sp. PH30583: Fermentation, Isolation, Structural Elucidation and Biological Activities.

The rare anishidiol and five new isochromans, including three novel dimers with unprecedented skeletons, were isolated from Stachybotrys sp. PH30583. Their structures were determined by spectral analyses. The bioactivities of these compounds were also investigated. The dimers (6-10) inhibited acetylcholinesterase at 50 µM, but the monomers did not. To investigate the biogenesis of the novel dimers, a time-course investigation of metabolite production was undertaken.

A new anthracycline from endophytic Streptomyces sp. YIM66403.

Species of Streptomyces are well known producers of diverse biological metabolites, and anthracyclines are one class of the typical antitumor antibiotics in drug studies. As one of the longest known antibiotics, anthracyclines have been received great attention frequently since its first discovery.1 Some of these anthracyclines have been used in medicine for the treatment of some cancers.2,3 Moreover, even in recent years, novel anthracyclines are constantly being discovered, such as aranciamycin anhydride.4 In our effort to search for new biological compounds from endophytes, a Streptomyces sp. YIM66403 producing special orange pigments caught our attention. Large-scale fermentation and subsequent fractionation of the extract of broth and mycelium proved that Streptomyces sp. YIM66403 was a strain yielding anthracyclines. As a result, we isolated a new anthracycline misamycin (1), together with η-pyrromycinone (2),5 4-Deoxy-ε-pyrromycinone (3)6 and other six known anthracyclines including cinerubin A (4),7 cinerubin B (5),7 antibiotic 80334 C (6),8 cinerubin X (7),9 collinemycin (8)10 and musettamycin (9)10 (Figure 1). Compound 1 showed cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS) method and anti-Staphylococcus aureus activity in comparison with other antimicrobial activity. The structure of misamycin (1) was established by various spectroscopic methods, whereas the structures of other known compounds (2–9) were confirmed by comparing their 1H and 13C-NMR data with these of compounds in the literature. In this paper, we would like to report the isolation, structure determination and biological activity of 1. The strain YIM66403 was isolated using glycerol-asparagine medium (1% glycerol, 0.1% asparagine, 0.1% dipotassium hydrogen phosphate, 1.2% agar, pH 7.2) from a healthy stem of the traditional Chinese medicinal plant Isodon eriocalyx obtained from Xishuangbanna, Yunnan, China, and was identified as Streptomyces sp. by 16S rRNA gene sequence. The seed medium consisted of 0.4% malt extract, 0.5% yeast extract, 0.5% glucose (adjusted to pH 7.2 before sterilization). Strain YIM66403 was cultured in 500ml erlenmeyer flasks each containing 200ml seed culture. After 4 days of incubation at 28 °C on a rotary shaker (125 r.p.m.), 10ml portion of the culture was inoculated into 1000ml erlenmeyer flasks each containing 250ml of fermentation medium consisting of 0.5% yeast extract, 2.4% soluble starch, 0.1% glucose, 0.3% beef extract, 0.3% peptone, 0.4% calcium carbonate (adjusted to pH 7.0 before sterilization). The fermentation was carried out at 28 °C on a rotary shaker (125 r.p. m.) for 8 days. A total of 100 l of fermentation broth was collected, and the broth and mycelium were separated. The broth was extracted with ethyl acetate, and the combined extracts were concentrated under reduced pressure to give the crude residue (23 g). The mycelium was extracted with acetone for 30min. The solvent was removed under vacuum and the remaining water phase was extracted with ethyl acetate; after concentration, 500 g oily crude extract was obtained. A flow diagram for the extraction of anthracyclines is shown in Scheme 1. Compound 1 was isolated as amorphous powder. A molecular ion peak m/z 656.2480 was observed based on the high-resolution MS analysis of 1 (calcd for C34H40O13, 656.2469), consistent with a molecular formula of C34H40O13. The 1H-1H COSY correlations from H-2 to H-3, H-7 to H-8 and HMBC correlations from 1-OH to C-1/2/ 12a, H-2 to C-4, H-3 to C-1, 4-OH to C-3/4/4a, 6-OH to C-5a/6/6a, H-7 to C-6/9, H-8 to C-10, H-10 to C-13, H-11 to C-10/12, H-14 to C-13 drew the skeleton of anthracycline for us. Then the 13C-NMR data comparison with its analog musettamycin (9)10 confirmed our conclusion. Compared the NMR data of compound 1 with that of musettamycin (9), it was found that N-CH3 and two CH (bearing respectively amino-group and hydroxyl ) were missing in 1, but two CH2 were additional in structure of 1, although the structure of 1 was similar to that of musettamycin, the two CH were replaced by CH2 in the structure of 1. The correlations of COSY and HMBC in compound 1 were determined in this elucidation (Figure 2). The C-1′ of rhodinose connected to C-7 was confirmed by the correlations from H-7 to C-1′ in HMBC. The COSY correlations from H-1′ to H-6′, and the HMBC correlations from H-6′ to C-4′, H-4′ to C-2′ confirmed that the oxygen atom was connected to C-4′, together with the COSY correlations from H-1′′ to H-6′′, and the HMBC correlations from

New megastigmane glycoside and alkaloids from Streptomyces sp. YIM 63342

New sesquiterpene glycoside, cyclodipeptide and piperidine derivative were isolated from Streptomyces sp. YIM 63342. On the basis of spectral data, their structures were determined as 3R, 5R, 6S, 7E, 9R-megastigman-7-en-3,5,6,9-tetrol-9-O-β-D-apiofuranosyl-(1   2)-β-D-glucopyranoside (1), cyclo (L-Pro-L-OMet) (2) and (R)-(E, E)-2-(l,3-pentadienyl) piperidine (3), together with three known compounds as N-acetyltyramine (4), lycoperodine-1 (5), cyclo(L-Pro-L-Tyr)(6).

New bioactive compounds from aquatic endophyte Chaetomium globosum

Abstract Two new oxidation products-related aureonitol and cytochalasan were isolated from Chaetomium globosum fermented in Chinese yam (Dioscorea opposita) and determined as 10,11-dihydroxyl- aureonitol (1) and yamchaetoglobosin A (2). Compound 2 indicated significant inhibitory effect on nitric oxide production in LPS-activated macrophages, anti-acetylcholinesterase activity with the inhibition ratios of 92.5, 38.2% at 50 μM, and cytotoxicity to HL-60, A-549, SMMC-7721, MCF-7 and SW480 with the range of inhibition ratio at 51–96% for a concentration of 40 μM. Compounds 1, 2 showed weak anticoagulant activity with PT at 16.8 s. Few work was reported on the anti-acetylcholinesterase, and anticoagulant activities of aureonitol, and cytochalasan derivatives. The preliminary structure–activity relationship stated that the oxidation ring-opening in yamchaetoglobosin A can retain the inhibitory effect against NO production and tumor cell.