Altersolanol A: a selective cytotoxic anthraquinone from a Phomopsis sp.

UNLABELLED: The cytotoxic compound Altersolanol A, an anthraquinone derivative was isolated from PM0409092 a fungus of Nyctanthes arbor-tristis (family Oleaceae). It was identified as a Phomopsis sp. by DNA amplification and sequencing of the ITS region. The chemical structure of Altersolanol A was elucidated from its physicochemical properties, 2D NMR spectroscopy and other spectroscopic data. The compound has in vitro cytotoxic activity against 34 human cancer cell lines with mean IC50 (IC70) values of 0.005 µg ml(-1) (0.024 µg ml(-1)) respectively. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage by Caspase-3 and -9 and by decreased anti-apoptotic protein expression. There are several previous reports of the anticancer activity of Altersolanol A, but we report here an extensive study using 36 cell lines which gives wider spectrum of results. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the cytotoxic potential of Altersolanol A isolated from the endophyte Phomopsis sp. (PM0409092) of the plant Nyctanthes arbor-tristis. The compound exhibits in vitro cytotoxicity against 34 human cancer cell lines with mean IC50 (IC70) value of 0.005 µg ml(-1) (0.024 µg ml(-1)). This is an in-depth report of Altersolanol A against a panel of 34 human cancer cell lines and extends observations from previous studies indicating that Altersolanol A can be used for the development of chemotherapeutics. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage of Caspase-3 and -9 and by decreased anti-apoptotic protein expression.

Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680.

UNLABELLED: A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead.

Anticancer activity of sclerotiorin, isolated from an endophytic fungus Cephalotheca faveolata Yaguchi, Nishim. & Udagawa.

Biodiversity provides critical support for drug discovery. A significant proportion of drugs are derived, directly or indirectly, from biological sources. Through high throughput screening (HTS) and bioassay-guided isolation, bioactive compound sclerotiorin has been isolated from an endophytic fungus Cephalotheca faveolata. Sclerotiorin was found to be potent anti-proliferative against different cancer cells. In this study sclerotiorin has been found to induce apoptosis in colon cancer (HCT-116) cells through the activation of BAX, and down-regulation of BCL-2, those further activated cleaved caspase-3 causing apoptosis of cancer cells.