Bioactive Dimeric Tetrahydroxanthones with 2,2'- and 4,4'-Axial Linkages from the Entomopathogenic Fungus Aschersonia confluens.

Abstract

Thirteen tetrahydroxanthone dimers, atrop-ascherxanthone A (1), ascherxanthones C-G (2-6), and confluxanthones A-G (7-13), were isolated from the entomopathogenic fungus Aschersonia confluens BCC53152. The chemical structures were determined based on analysis of NMR spectroscopic and mass spectrometric data. The absolute configurations of compounds 1 and 7 were confirmed by single-crystal X-ray diffraction experiments, while the configurations of other compounds were assigned based upon evidence from NOESY and NOEDIFF experiments, modified Mosher's method, and ECD spectroscopic data together with biogenetic considerations. Compounds 1, 3-5, 7-11, and 13 showed antimalarial activity against Plasmodium falciparum (K1, multidrug-resistant strain) (IC50 0.6-6.1 μM), antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC 6.3-25.0 μg/mL), and cytotoxicity against NCI-H187 (IC50 0.5-3.5 μM) and Vero (IC50 0.9-6.1 μM) cells. All tested compounds except for compound 9 exhibited cytotoxicity against KB cells (IC50 1.3-9.7 μM).