Enhanced Production and Anticancer Properties of Photoactivated Perylenequinones.

ABSTRACT

Hypocrellins and hypomycins are naturally occurring fungal perylenequinones with potential photodynamic activity against cancer and microbial diseases. This project pursued three lines of research. First, the production of perylenequinones was enhanced by investigating the effect of culture medium and light exposure on their biosynthesis. Solid-fermentation cultures on rice medium allowed for enhanced production of hypocrellins as compared to Cheerios or oatmeal medium. Alternatively, increased production of hypomycins, which are structurally related to the hypocrellins, was observed on oatmeal medium. In both cases, light exposure was an essential factor for the enhanced biosynthesis. In addition, this led to the discovery of two new perylenequinones, ent-shiraiachrome A (5) and hypomycin E (8), which were elucidated based on spectroscopic data. Finally, the photocytotoxic effects of both classes of compounds were evaluated against human skin melanoma, with EC50 values at nanomolar levels for hypocrellins and micromolar levels for hypomycins. In contrast, both classes of compounds showed reduced dark toxicity (EC50 values >100 µM), demonstrating promising phototherapeutic indices.