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

doi:10.1021/acs.jnatprod.6b00948

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

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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 language	English
Pages (from-to)	2-11
Number of pages	10
Journal	Journal of Natural Products
Volume	80
Issue number	1
DOIs	https://doi.org/10.1021/acs.jnatprod.6b00948
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.jnatprod.6b00948

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Shaaban, K. A., Saunders, M. A., Zhang, Y., Tran, T., Elshahawi, S. I., Ponomareva, L. V., Wang, X., Zhang, J., Copley, G. C., Sunkara, M., Kharel, M. K., Morris, A. J., Hower, J. C., Tremblay, M. S., Prendergast, M. A., & Thorson, J. S. (2017). Spoxazomicin D and Oxachelin C, potent neuroprotective carboxamides from the appalachian coal fire-associated isolate streptomyces sp. RM-14.6. Journal of Natural Products, 80(1), 2-11. https://doi.org/10.1021/acs.jnatprod.6b00948

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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.",

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

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: {\textcopyright} 2016 American Chemical Society and American Society of Pharmacognosy.",

year = "2017",

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doi = "10.1021/acs.jnatprod.6b00948",

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Shaaban, KA, Saunders, MA, Zhang, Y, Tran, T, Elshahawi, SI, Ponomareva, LV, Wang, X, Zhang, J, Copley, GC, Sunkara, M, Kharel, MK, Morris, AJ, Hower, JC, Tremblay, MS, Prendergast, MA & Thorson, JS 2017, 'Spoxazomicin D and Oxachelin C, potent neuroprotective carboxamides from the appalachian coal fire-associated isolate streptomyces sp. RM-14.6', Journal of Natural Products, vol. 80, no. 1, pp. 2-11. https://doi.org/10.1021/acs.jnatprod.6b00948

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T1 - Spoxazomicin D and Oxachelin C, potent neuroprotective carboxamides from the appalachian coal fire-associated isolate streptomyces sp. RM-14.6

AU - Shaaban, Khaled A.

AU - Saunders, Meredith A.

AU - Zhang, Yinan

AU - Tran, Tuan

AU - Elshahawi, Sherif I.

AU - Ponomareva, Larissa V.

AU - Wang, Xiachang

AU - Zhang, Jianjun

AU - Copley, Gregory C.

AU - Sunkara, Manjula

AU - Kharel, Madan K.

AU - Morris, Andrew J.

AU - Hower, James C.

AU - Tremblay, Matthew S.

AU - Prendergast, Mark A.

AU - Thorson, Jon S.

N1 - 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.

PY - 2017/1/27

Y1 - 2017/1/27

N2 - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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