Conglobatins B–E: cytotoxic analogues of the C2-symmetric macrodiolide conglobatin

Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces , distinct from reported conglobatin producer, Streptomyces conglobatus ATCC 31005. Conglobatins B–E diverge from conglobatin through differing patterns of methylation on the macrodiolide skeleton. The altered methyl positions suggest a deviation from the published biosynthetic pathway, which proposed three successive methylmalonyl-CoA extender unit additions to the conglobatin monomer. Conglobatins B1, C1 and C2 exhibited more potent cytotoxic activity selectively against the NS-1 myeloma cell line (IC 50 0.084, 1.05 and 0.45 µg ml −1 , respectively) compared with conglobatin (IC 50 1.39 µg ml −1 ).