Bacillus amyloliquefaciens induces production of a novel blennolide K in coculture of Setophoma terrestris.

AIMS: The discovery of known bioactive chemical leads from microbial monocultures hinders the efficiency of drug discovery programmes. Therefore, in recent years, the use of fungal-bacterial coculture experiments has gained considerable attention due to their ability to generate new bioactive leads. In this work, fungal strain Setophoma terrestris was cocultured with Bacillus amyloliquifaciens to discover novel bioactive compounds. MATERIALS AND METHODS: The bioactive methanolic coculture extract was chosen for the isolation of compounds by chromatographic methods. The isolated compounds were characterized by NMR and mass spectrometric techniques. CONCLUSION: Coculture extract has resulted in the production of five blennolides. The novel compound, blennolide K was found active against PC-3 (prostate) and MCF-7 (breast) cell lines with an IC50 value of 3·7 ± 0·6 and 4·8 ± 0·4 µmol l-1 respectively. Furthermore, the nuclear morphology study in PC-3 cells after treatment with blennolide K, demonstrated chromatin condensation, formation of apoptotic bodies and shrinkage of cells. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, only few studies have reported the induction of bioactive compounds by coculture having long-distance inhibition morphology. This is principally due to the low occurrences of such morphology. Our study demonstrates the impact of coculture on production of new chemical leads in drug discovery programmes.

New cytochalasin from Rosellinia sanctae-cruciana, an endophytic fungus of Albizia lebbeck.

AIM: To explore the potential of Rosellinia sanctae-cruciana an endophytic fungus associated with Albizia lebbeck for pharmaceutically important cytotoxic compounds. METHODS AND RESULTS: One novel cytochalasin, named jammosporin A (1) and four known analogues (2-5) were isolated from the culture of the endophytic fungus R. sanctae-cruciana, harboured from the leaves of the medicinal plant A. lebbeck. Their structures were elucidated by extensive spectroscopic analyses including one-dimensional and two-dimensional nuclear magnetic resonance data along with MS data and by comparison with literature reports. In preliminary screening the ethyl acetate extract of the fungal culture was tested for cytotoxic activity against a panel of four cancer cell lines (MOLT-4, A549, MIA PaCa-2 and MDA-MB-231), and found to be active against MOLT-4 with an IC50 value of 10 µg ml-1 . Owing to the remarkable cytotoxic activity of the extract the isolated compounds (1-5) were evaluated for their cytototoxicity against the MOLT-4 cell line by MTT assay. Interestingly, compounds 1-2, 4 and 5 showed considerable cytotoxic potential against the human leukaemia cancer cell line (MOLT-4) with IC50 values of 20·0, 10·0, 8·0 and 6·0 µmol l-1 , respectively, while compound 3 showed an IC50 value of 25 µmol l-1 . This is the first report of the existence of this class of secondary metabolites in R. sanctae-cruciana fungus. CONCLUSION: This study discovered a novel compound, named jammosporin A, isolated for the first time from R. sanctae-cruciana, an endophytic fungus of A. lebbeck with anticancer activity against the MOLT-4 cell line. SIGNIFICANCE AND IMPACT OF THE STUDY: Rosellinia sanctae-cruciana represents an interesting source of a new compound with bioactive potential as a therapeutic agent against a human leukaemia cancer cell line (MOLT-4).