title: Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6.
abstract: The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6-8] and 11 previously reported bacterial metabolites (1, 3, 9-12a, and 14-18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Shaaban
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Saunders
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: California Institute for Biomedical Research (Calibr) , La Jolla, California 92037, United States.
authors.forename: Tuan
authors.initials: T
authors.lastname: Tran
authors.forename: Sherif I
authors.initials: SI
authors.lastname: Elshahawi
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Ponomareva
authors.forename: Xiachang
authors.initials: X
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Applied Energy Research, University of Kentucky , Lexington, Kentucky 40511, United States.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Copley
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.affiliation: School of Pharmacy, University of Maryland Eastern Shore , Princess Anne, Maryland 21853, United States.
authors.forename: Madan K
authors.initials: MK
authors.lastname: Kharel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.affiliation: Center for Applied Energy Research, University of Kentucky , Lexington, Kentucky 40511, United States.
authors.forename: James C
authors.identifier: 0000-0003-4694-2776
authors.initials: JC
authors.lastname: Hower
authors.affiliation: California Institute for Biomedical Research (Calibr) , La Jolla, California 92037, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Tremblay
authors.forename: Mark A
authors.initials: MA
authors.lastname: Prendergast
authors.forename: Jon S
authors.identifier: 0000-0002-7148-0721
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001061:Appalachian Region; D003031:Coal; D004987:Ethers / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010080:Oxazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003031:Coal; D004987:Ethers; C000594031:MBJ-0034; C000594032:MBJ-0035; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010080:Oxazoles; D010455:Peptides; D010636:Phenols; C516693:oxachelin; C000621482:spoxazomicin D; C011580:A-130A