Antibacterial and Cytotoxic Actinomycins Y6-Y9 from Streptomyces sp. Strain Gö-GS12

Document Type

Article

Publication Date

10-13-2016

Abstract

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.

Comments

This article was originally published in Journal of Natural Products, volume 79, issue 10, in 2016. https://doi.org/10.1021/acs.jnatprod.6b00742

Copyright

American Chemical Society and American Society of Pharmacognosy

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