Arugosins G and H:  Prenylated Polyketides from the Marine-Derived Fungus Emericella nidulans var. acristata

Abstract

The fungus Emericella nidulans var. acristata was isolated as an endophyte from a Mediterranean green alga. Cultivation of this fungus yielded two new compounds, arugosins G (1) and H (2), together with the known metabolites 3-9. Arugosins (1-4) are benzophenone derivatives, biosynthetically related to the xanthones 5, 6, and 9. The indole alkaloid 7 displayed antitumor activity in a panel of 36 human tumor cell lines, exhibiting a mean IC(50) value of 5.5 microg/mL in an in vitro survival and proliferation assay. Furthermore, compounds 3 and 4 showed moderate antitumor activity toward individual tumor cell lines. None of compounds 1-8 exhibited any immunostimulatory activity assessed as the capacity to induce cytokines in PBMCs from healthy donors.

Fungal metabolites: structural diversity as incentive for anticancer drug development

“…From this fungus we obtained several benzophenone derivatives, named arugosins, and the indol alkaloid emindole DA ( Fig. 12; Kralj et al 2006). Arugosins A and B showed moderate cytotoxic activity in seven out of the 36 human tumor cell lines.…”

Fungal secondary metabolites – Strategies to activate silent gene clusters

“…Examples are the isolation of the arugosins from the marinederived fungus Emericella nidulans var. acristata (Kralj et al, 2006) or the finding of deoxypodophyllotoxin, a pro-drug of the anticancer drug podophyllotoxin, in the endophytic fungus Aspergillus fumigatus Fresenius (Kusari et al, 2009).…”

Endophytic Fungi: Novel Sources of Anticancer Molecules

“…Fungal endophytes are a diverse and versatile group of microorganisms that colonize plants in the Arctic and Antarctic, and in geothermal soils, deserts, oceans, rainforests, mangrove swamps, and coastal forests (Fisher et al 1995 ;Regina et al 2002 ;Strobel 2002 ;Bashyal et al 2005 ;Suryanarayanan et al 2005 ;Wang et al 2006 ;Lin et al 2008a , b ;Rosa et al 2009 ). They have been isolated from the root complexes and aerial parts of a diverse range of hosts including algae, bryophytes, pteridophytes, gymnosperms, and angiosperms (Swatzell et al 1996 ;Wang et al 2006 ;Kralj et al 2006 ;Gond et al 2007 ;Silvia et al 2008 ;Hoffman and Arnold 2008 ;Kharwar et al 2008 ). Fungal endophytes are an important component of microbial biodiversity.…”

“…Indole alkaloid emindole DA was isolated from Emericella nidulans var. acristata , an endophyte of unspecifi ed Mediterranean green alga (Kralj et al 2006 ). It exhibited antitumor activity against 36 human tumor cell lines representing 11 different tumor types, with a mean IC 50 value of 5.5 μg/mL compared to the reference compound Adriamycin tested in parallel in the same assays with an IC 50 value of 0.16 μg/mL (Kralj et al 2006 ).…”

“…Arugosins A and B are benzophenone polyketides isolated from Eme ricella nidulans var. acristata , an endophyte of a Mediterranean green alga (Kralj et al 2006 ). Both compounds showed (Zhan et al 2007 ).…”