Trichodermadiones A and B from the solid culture of Trichoderma atroviride S361, an endophytic fungus in Cephalotaxus fortunei.

Chemical investigation on the solid rice culture of Trichoderma atroviride S361, an endophyte isolated from Cephalotaxus fortunei, has afforded a pair of novel N-furanone amide enantiomers, (-)-trichodermadione A (1a) and (+)-trichodermadione A (1b), and a new cyclohexenone sesquiterpenoid, trichodermadione B (2), together with six known secondary metabolites. Chiral separation of compound 1 was successfully performed on a Lux Cellulose-2 column. Their structures were elucidated by detailed spectroscopic analyses on the basis of NMR, HRMS, and ECD data, and the absolute configurations of the new compounds were determined by computational analyses of their electronic circular dichroism (ECD) spectra and Snatzke's method. Compounds 1a, 1b and 2 were also evaluated for their cytotoxicity against DU145 and PC3 cell lines, as well as inhibitory effects against the production of NO in LPS-stimulated RAW264.7 cells.

Antimicrobial and antitumor activity and diversity of endophytic fungi from traditional Chinese medicinal plant Cephalotaxus hainanensis Li.

Endophytes from Cephalotaxus hainanensis Li, an important source of anti-leukemia drugs, have not been widely explored. In this study, 265 endophytic fungal isolates from C. hainanensis Li were screened for antimicrobial activities against tilapia, banana, rice, and rape and for antitumor activities against human leukemia cell lines (K562, NB4, and HL-60). Diversity was also analyzed. The results showed that 17.7% of the endophytic fungi had antimicrobial activities against at least three different test microbes, and activity against Fusarium oxysporum RKY102 was the highest at 15.8%. Cytotoxicity against at least one tumor cell line tested was observed in 18.5% of the endophytic fungi; with the highest value of 10.6% against K562. The endophytic fungal strains also showed relatively high activities against K562, NB4, and HL-60 while relatively fewer strains were cytotoxic against the human hepatic Hep-G2 and colon LoVo cancer cell lines. Thirty endophytic fungal strains showed both high antimicrobial and antitumor activities. Moreover, the analyses of the diversity of the 30 highly active strains showed they belonged to 20 species from 14 genera, and this is the first report of endophytic fungi Albonectria rigidiuscula, Colletotrichum magnisporum, and Nemania diffusa being isolated from Cephalotaxus plants. These findings suggest that natural antibacterial products for humans and tilapia; antifungal compounds for rice, rape, and banana; and antitumor compounds for leukemia therapy could be isolated from fungal strains derived from C. hainanensis Li.

Diversity and antimicrobial activity of endophytic fungi isolated from Cephalotaxus hainanensis Li, a well-known medicinal plant in China.

UNLABELLED: About 1051 endophytic fungi were isolated from leaves, branches, barks and stems of Cephalotaxus hainanensis Li from four sites in Hainan, China. The fungi were identified as 21 genera by morphology and ITS sequences. One dominant species was Phomopsis quercella in Hainan Tropical Botanical Garden and Bawangling Nature Reserve, with relative frequency of 42·06 and 34·88% respectively. Another dominant species was Colletotrichum boninense in Wuzhishan and Jianfengling Nature Reserves, with relative frequency of 36·84 and 46·97% respectively. Among the selected 21 endophytic fungi, 17 strains (80·95%) had activity against at least one pathogenic bacteria, and 14 strains (66·67%) exhibited activity against at least one fungal pathogens. Neonectria macroconidialis showed strong inhibition against Staphylococcus aureus (inhibition zone being 20 mm), Bacillus subtilis (14 mm) and Streptococcus agalactiae (28 mm). Xylaria sp. showed strong inhibition against Escherichia coli (20 mm), Rhizoctonia solani (20 mm) and Sclerotinia sclerotiorum (17 mm). Verticillium bulbillosum showed great activity against Strep. agalactiae (32 mm) and Fusarium oxysporum (22 mm). These endophytic fungi showed potentials in medicine development. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi from medicinal plants are an important source of novel and viable drugs. Cephalotaxus hainanensis Li is well known for leukaemia treatment and its endophytic fungi were isolated to investigate the diversity and antimicrobial activity. It was found that Ce. hainanensis Li had rich endophytic fungi, and some fungi showed strong antimicrobial activity against certain pathogens. These fungi can be used in medicine development.

Aromatic compounds from endophytic fungus Colletotrichum sp. L10 of Cephalotaxus hainanensis Li.

Six aromatic compounds were isolated from the endophytic fungus Colletotrichum sp. of Cephalotaxus hainanensis Li [Cephalotaxus mannii Hook. f.]. Their structures were determined on the basis of chemical and spectroscopic methods. The compound 2 was the enantiomer of compound 1. The compound 4 was the epimeride of the compound 3. The compounds 1, 2, 4 and 5 were evaluated for cytostatic activity against HL-60 and PC-3 cells.

Sesquiterpenoids from Trichoderma atroviride, an endophytic fungus in Cephalotaxus fortunei.

Two new sesquiterpenoids, identified as (rel 1S, 3R, 4R, 7R)-3-[5-hydroxy-4-methylpent-3-enyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (1) and (rel 1S, 3R, 4R, 7R)-3-[3, 4-dihydroxy-4-methylpentyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (2), were isolated from cultures of Trichoderma atroviride (strain no. S361), an endophytic fungal strain residing in the bark of Cephalotaxus fortunei. The structures of compounds 1 and 2 were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Both compounds 1 and 2 were potent inhibitors on NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 15.3 and 9.1µM, respectively.

A new 5-acyl-2-methylpyrrole from the endophytic fungus S20 of Cephalotaxus hainanensis.

A new 5-acyl-2-methylpyrrole, isolated from the endophytic fungus S20 of Cephalotaxus hainanensis, was elucidated as 1-(5-methyl-1H-pyrrol-2-yl)-2-((2S*,3R*)-3-((E)-prop-1-enyl)oxiran-2-yl)ethanone (1) on the basis of spectroscopic evidence, including 1D- and 2D-NMR (HMQC, 1H-1H COSY, HMBC and ROESY) and MS analysis. Compound 1 showed inhibitory effects on Staphylococcus aureus and methicillin-resistant S. aureus by the filter paper disc agar diffusion method.