Saliniquinones A-F, New Members of the Highly Cytotoxic Anthraquinone-γ-Pyrones from the Marine Actinomycete Salinispora arenicola

Abstract

Six new anthraquinone-γ-pyrones, saliniquinones A-F (1-6), which are related to metabolites of the pluramycin/altromycin class, were isolated from a fermentation broth of the marine actinomycete Salinispora arenicola (strain CNS-325). Their structures were determined by analysis of one- and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data. The relative and absolute configurations of compounds 1-6 were determined by analysis of NOESY NMR spectroscopic data and by comparison of circular dichroism and optical rotation data with model compounds found in the literature. Saliniquinone A (1) exhibited potent inhibition of the human colon adenocarcinoma cell line (HCT-116) with an IC₅₀ of 9.9 × 10^-9 M. In the context of the biosynthetic diversity of S. arenicola, compounds 1-6 represent secondary metabolites that appear to be strain specific and thus occur outside of the core group of compounds commonly observed from this species.

Fig. 1

Structures of saliniquinones A–F (1–6).

Fig. 2

Key COSY and HMBC NMR correlations for saliniquinone A (1).

Fig. 3

NOE correlations and potential C-16 configurations of saliniquinone C (3).