Bioactivity-guided fractionation of metabolites from the crinoid Holopus rangii led to the discovery of two new phenanthroperylenequinone derivatives, gymnochromes E (1) and F (2). Gymnochrome E showed cytotoxic activity toward the NCI/ADR-Res with an IC(50) of 3.5 microM. It also inhibited histone deacetylase-1 with an IC(50) of 3.3 microM. Gymnochrome F was a moderate inhibitor of myeloid cell leukemia sequence 1 (MCL-1) binding to Bak. Two anthraquinone metabolites, emodic acid (4) and its new bromo derivative (5), were also isolated from the crinoid and show remarkable similarity to the phenanthroperylenequinone core, suggesting that these metabolites share the same polyketide biosynthetic pathway.