Globosuxanthone A

During our investigation on the endophytic fungi of Azadirachta indica, the strain YM 311593 was obtained from the fruit of the plant. The culture extract of the strain showed antifungal activities against four phytopathogenic fungi. Based on the morphological features and phylogenetic definition, the strain YM 311593 was identified as Paraconiothyrium sp. Four xanthones and one anthraquinone were obtained from the extract of the fermentation broth of the strain. They were characterized to be globosuxanthone A (1), vertixanthone (2), hydroxyvertixanthone (3), 3,8-dihydroxy-1-methy1-9H- xanthen-9-one (4), and danthron (5), respectively, by spectroscopic elucidation. Furthermore, the absolute configuration of 1 was deduced by X-ray diffraction analysis. Besides, compound 4 was firstly found from natural sources. The antifungal activities of compounds 1-5 towards four phytopathogens were assayed using broth microdilution method. Among them, globosuxanthone A (1) showed obvious antifungal activity towards Fusarium graminearum, Fusarium solani, and Botrytis cinerea with MIC values of 4, 8, and 16 μg/mL, respectively.

1-Hydroxy-10-methoxy-dibenz[b,e]oxepin-6,11-dione (1) was obtained from the culture broth of a marine-derived fungus, Beauveria bassiana TPU942, isolated from a marine sponge collected at Iriomote Island in Okinawa, together with two known compounds, chrysazin (2) and globosuxanthone A (3). The structure of 1 was elucidated on the basis of its spectroscopic data (HREIMS, 1D and 2D NMR experiments including ¹H--¹H COSY, HMQC and HMBC spectra). Dibenz[b,e]oxepines are rare in nature, and only six natural products have been reported. Therefore, compound 1 is the seventh natural product in this class. Compounds 2 and 3 showed an antifungal activity against Candida albicans, and 3 inhibited the cell growth against two human cancer cell lines, HCT-15 (colon) and Jurkat (T-cell lymphoma). Compound 1 did not show an apparent activity in the same bioassays.

Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xanthones, globosuxanthone C (3) and D (4), 2-hydroxyvertixanthone (5), and two known anthraquinones (6 and 7). The structures of the new compounds 1-4 were elucidated by NMR and MS techniques, and the relative stereochemistry of 1 was determined by X-ray crystallographic analysis. Of the compounds encountered, 1 was found to exhibit strong cytotoxicity against a panel of seven human solid tumor cell lines, disrupt the cell cycle leading to the accumulation of cells in either G2/M or S phase, and induce classic signs of apoptosis.