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

Chemical investigation of a previously unreported indigenous AustralianStreptomycesstrain 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 ofStreptomyces, distinct from reported conglobatin producer,Streptomyces conglobatusATCC 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 mu g ml(-1), respectively) compared with conglobatin (IC(50)1.39 mu g ml(-1)).