title: Antibacterial and Cytotoxic Actinomycins Y6-Y9and Zp from Streptomyces sp. Strain Gö-GS12.
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), which 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 2-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 nonrearranged comparator actinomycin Y5and other actinomycins.
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Xiachang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Sherif I
authors.initials: SI
authors.lastname: Elshahawi
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Ponomareva
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: McErlean
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Arlinghaus
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.affiliation: Department of Pharmaceutical Sciences and ‡Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Van Lanen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002470:Cell Survival; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry*; D013912:Threonine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D003609:Dactinomycin; C011285:hydroxythreonine; D013912:Threonine; D011392:Proline