Spoxazomicin D and Oxachelin C, potent neuroprotective carboxamides from the appalachian coal fire-associated isolate streptomyces sp. RM-14.6

Khaled A. Shaaban, Meredith A. Saunders, Yinan Zhang, Tuan Tran, Sherif I. Elshahawi, Larissa V. Ponomareva, Xiachang Wang, Jianjun Zhang, Gregory C. Copley, Manjula Sunkara, Madan K. Kharel, Andrew J. Morris, James C. Hower, Matthew S. Tremblay, Mark A. Prendergast, Jon S. Thorson

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish
Pages (from-to)2-11
Number of pages10
JournalJournal of Natural Products
Volume80
Issue number1
DOIs
StatePublished - Jan 27 2017

Bibliographical note

Funding Information:
This work was supported in part by NIH T32 DA016176 (Y.Z.), the University of Kentucky College of Pharmacy, the

Publisher Copyright:
© 2016 American Chemical Society and American Society of Pharmacognosy.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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