Sorbicillinoid Analogues with Cytotoxic and Selective Anti-Aspergillus Activities from Scytalidium album

As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, eleven compounds were isolated and identified from an organic extract of the fungus Scytalidium album (MSX51631) using bioactivity-directed fractionation against human cancer cell lines. Of these, eight were a series of sorbicillinoid analogues (1–8), of which four were new [scalbucillin A (2), scalbucillin B (3), scalbucillin C (6), and scalbucillin D (8)], two were phthalides (9–10), and one was naphthalenone (11). Compounds (1–11) were tested in the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compound 1 was the most potent with IC(50) values of 1.5 and 0.5 μM, respectively, followed by compound 5, with IC(50) values of 2.3 and 2.5 μM at 72 h. Compound 1 showed a 48-h IC(50) value of 3.1 μM when tested against the lymphocytic leukemia cell line OSU-CLL, while the nearly identical compound 5 had almost no activity in this assay. Compounds 1 and 5 showed selective and equipotent activity against Aspergillus niger with minimum inhibitory concentration values of 0.05 and 0.04 μg/ml (0.20 and 0.16 μM), respectively. The in vitro hemolytic activity against sheep erythrocytes of compounds 1 and 5 was investigated and were found to provoke 10% hemolysis at 52.5 and 45.0 μg/ml, respectively, indicative of a promising safety factor.