Cytotoxic and Protein Kinase Inhibiting Nakijiquinones and Nakijiquinols from the Sponge <i>Dactylospongia metachromia</i>

Abstract

Chemical investigation of the sponge <i>Dactylospongia metachromia</i> afforded five new sesquiterpene aminoquinones (<b>1</b>–<b>5</b>), two new sesquiterpene benzoxazoles (<b>6</b> and <b>7</b>), the known analogue 18-hydroxy-5-<i>epi</i>-hyrtiophenol (<b>8</b>), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds <b>1</b>–<b>5</b> showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC₅₀ values ranging from 1.1 to 3.7 μM. When tested <i>in vitro</i> for their inhibitory potential against 16 different protein kinases, compounds <b>5</b>, <b>6</b>, and <b>8</b> exhibited the strongest inhibitory activity against ALK, FAK, IGF1-R, SRC, VEGF-R2, Aurora-B, MET wt, and NEK6 kinases (IC₅₀ 0.97–8.62 μM)