Actinoplanones B

Two new cytotoxic polycyclic xanthones, actinoplanones A (1) and B (2) were isolated from the culture broth of Actinoplanes sp. R-304 by monitoring their bioactivity against HeLa cells. Compound 1 was extremely cytotoxic (IC50 0.00004 micrograms/ml) against HeLa cells. The structures of 1 and 2 were established mainly by analyses of 2D heteronuclear correlation NMR experiments. The absolute configurations of the asymmetric carbons of the compounds have been assigned to be 9R, 24S, 25R and 27S by circular dichroism spectra and NMR analysis using chiral derivatives (esters of alpha-methoxy-alpha-(trifluoromethyl)acetic acid).

Our previous finding of strong cytotoxic polycyclic xanthones, actinoplanones A (1) and B (2), in the culture broth of Actinoplanes sp. R-304 stimulated us to isolate further five new cytotoxic polycyclic xanthones which were named actinoplanones C (3), D (4), E (5), F (6) and G (7) from the broth. Actinoplanones C (3) and G (7) showed very strong cytotoxicity against HeLa cells at less than 0.00004 microgram/ml dosage (IC50). The structures of 3-7 were varieties of 1 for the N-2 and C-4 substituents. All or several actinoplanones showed strong antimicrobial activities against bacteria and the rice blast fungus. Actinoplanone A (1) was tested for cytotoxicity against various tumor cells and for inhibitory effect on HeLa cell macromolecular synthesis, and 1 exhibited strong cytotoxicity against the cells and inhibitory action on DNA synthesis.