Antibacterial and Cytotoxic Actinomycins Y6-Y9 from Streptomyces sp. Strain Gö-GS12
Four new Y-type actinomycin analogues named Y6–Y9 (1–4) were isolated and characterized from the scale up fermentation of the Streptomyces sp. strain Gö-GS12, as well as actinomycin Zp (5) that was, for the first time, isolated as a natural product. Structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and HRMS. The 4-hydroxythreonine on the β-ring of 1 uniquely undergoes both a rearrangement by a two-fold acyl shift and an additional ring closure with the amino group of the phenoxazinone chromophore, and the α-rings of 4 and 5 contain a rare 5-methyl proline. Compounds 2–5 showed potent antibacterial activities against Gram-positive bacteria that correlated with cytotoxicity against representative human cell lines. The combination of a β-ring rearrangement and additional ring closure in 1 rendered this actinomycin significantly less potent relative to the non-rearranged comparator actinomycin Y5 and other actinomycins.
Wenlong C, Wang X, Elshahawi SI, et al. Antibacterial and cytotoxic actinomycins Y6-Y9 from Streptomyces sp. strain Gö-GS12. J Nat Prod. 2016;79(10):2731-2739. https://doi.org/10.1021/acs.jnatprod.6b00742
American Chemical Society and American Society of Pharmacognosy