A CYTOTOXIC PYRANONAPHTHOQUINONE FROM CULTURED LICHEN MYCOBIONTS OF HAEMATOMMA sp

Spore-derived mycobionts of the lichen Haematomma sp. were cultivated on malt-yeast extract medium supplemented with 10% sucrose to produce a new pyranonaphthoquinone, 4, as well as two known compounds (-)-usnic acid (2) and 5-deoxy-7-methylbostrycoidin (3). The structure of 4 was determined by spectroscopic methods. The inhibitory activities of 3, 4, and 6–8 against mammalian DNA polymerases (pols) and cytotoxic effects against a HeLa human cervical cancer cell line were also evaluated. Compound 4 showed the strongest mammalian pol inhibitory activity and cytotoxicity (ID50 = 6.7 μM) among the tested compounds. Isolation and cultivation of mycobionts from the spores of lichen thalli could provide new sources of biologically active compounds. Lichens, which are symbiotic organisms of fungi (mycobiont) and algae (photobiont), are well known to produce characteristic secondary metabolites such as depsides, depsidones, dibenzofurans, and γ-lactones, so-called lichen substances. Some lichen substances have been found to exhibit a wide range of potentially useful biological activities. Some of these secondary metabolites from lichen thalli are also produced by isolated cultured mycobionts of lichens without the participation of their photobionts. Furthermore, cultured lichen mycobionts have the ability under osmotically stressed conditions to produce unusual substances that have never been detected in the lichenized state, and some of the metabolites showed significant biological activities. Based on our interests in the biological activities of the metabolites from cultured lichen mycobionts, we re-investigated the metabolites of Haematomma sp. 1728 HETEROCYCLES, Vol. 94, No. 9, 2017