Isoswinholide B and swinholide K, potently cytotoxic dimeric macrolides from Theonella swinhoei

Abstract

Chemical investigation of an Indonesian specimen of Theonella swinhoei afforded the new dimeric macrolides isoswinholide B (5) and swinholide K (6), along with the known swinholides A (1), B (2) and D (3) and isoswinholide A (4). Isoswinholide B showed an unprecedented 21/19' lactonization pattern, while swinholide K included an sp(2) methylene attached at C-4 and an additional oxymethine group at C-5, whose configuration has been determined through application of J-based configuration analysis. The isolated swinholides (1-6), with the exception of isoswinholide B, showed a cytotoxic activity on HepG2 (hepatocarcinoma cell line) in the nanomolar range.

Keywords: Actin-binding cytotoxins; Macrolides; Swinholides; Theonella swinhoei.