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Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells

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Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells. / Forget, Stephanie M; Robertson, Andrew W; Hall, Steven R et al.
In: The Journal of antibiotics, Vol. 71, No. 8, 26.04.2018, p. 722-730.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Forget, SM, Robertson, AW, Hall, SR, MacLeod, JM, Overy, DP, Kerr, RG, Goralski, KB & Jakeman, DL 2018, 'Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells', The Journal of antibiotics, vol. 71, no. 8, pp. 722-730. https://doi.org/10.1038/s41429-018-0060-0

APA

Forget, S. M., Robertson, A. W., Hall, S. R., MacLeod, J. M., Overy, D. P., Kerr, R. G., Goralski, K. B., & Jakeman, D. L. (2018). Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells. The Journal of antibiotics, 71(8), 722-730. https://doi.org/10.1038/s41429-018-0060-0

Vancouver

Forget SM, Robertson AW, Hall SR, MacLeod JM, Overy DP, Kerr RG et al. Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells. The Journal of antibiotics. 2018 Apr 26;71(8):722-730. doi: 10.1038/s41429-018-0060-0

Author

Forget, Stephanie M ; Robertson, Andrew W ; Hall, Steven R et al. / Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells. In: The Journal of antibiotics. 2018 ; Vol. 71, No. 8. pp. 722-730.

Bibtex

@article{40e3aa31fe9b465aa38de81ee04807a2,
title = "Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells",
abstract = "Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1) obtained from a culture of S. venezuelae ISP5230 with L-ornithine (Orn). 1 arises from the rearrangement of a putative five-membered ring containing jadomycin incorporating Orn, whereby intramolecular attack of the E-ring carbonyl from the δ-NH2 group of the Orn side chain results in collapse of the oxazolone ring and formation of a stable six-membered lactam. This rearrangement produces a jadomycin with a 3a hemiaminal position that is susceptible to solvolysis. A structure-activity relationship is discussed based on the antimicrobial activity of 1 compared to previously reported jadomycins, providing evidence that the presence of a 3a hemiaminal enhances activity against Gram-positive bacteria. Additionally, assays to quantify reactive oxygen species (ROS) generation and cell viability were performed using a series of nine jadomycins. Compound 1 was found to produce the highest ROS activity and to possess the greatest cytotoxicity against MDA-MB-231 breast cancer cells.",
keywords = "Anti-Bacterial Agents/pharmacology, Antineoplastic Agents/pharmacology, Cell Line, Tumor, Cell Survival/drug effects, Drug Resistance, Neoplasm, Humans, Isoquinolines/chemistry, Microbial Sensitivity Tests, Ornithine/chemistry, Reactive Oxygen Species/metabolism, Staphylococcus/drug effects, Streptomyces/metabolism, Structure-Activity Relationship, Triple Negative Breast Neoplasms/drug therapy",
author = "Forget, {Stephanie M} and Robertson, {Andrew W} and Hall, {Steven R} and MacLeod, {Jeanna M} and Overy, {David P} and Kerr, {Russell G} and Goralski, {Kerry B} and Jakeman, {David L}",
year = "2018",
month = apr,
day = "26",
doi = "10.1038/s41429-018-0060-0",
language = "English",
volume = "71",
pages = "722--730",
journal = "The Journal of antibiotics",
issn = "0021-8820",
publisher = "Japan Antibiotics Research Association",
number = "8",

}

RIS

TY - JOUR

T1 - Isolation of a jadomycin incorporating L-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells

AU - Forget, Stephanie M

AU - Robertson, Andrew W

AU - Hall, Steven R

AU - MacLeod, Jeanna M

AU - Overy, David P

AU - Kerr, Russell G

AU - Goralski, Kerry B

AU - Jakeman, David L

PY - 2018/4/26

Y1 - 2018/4/26

N2 - Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1) obtained from a culture of S. venezuelae ISP5230 with L-ornithine (Orn). 1 arises from the rearrangement of a putative five-membered ring containing jadomycin incorporating Orn, whereby intramolecular attack of the E-ring carbonyl from the δ-NH2 group of the Orn side chain results in collapse of the oxazolone ring and formation of a stable six-membered lactam. This rearrangement produces a jadomycin with a 3a hemiaminal position that is susceptible to solvolysis. A structure-activity relationship is discussed based on the antimicrobial activity of 1 compared to previously reported jadomycins, providing evidence that the presence of a 3a hemiaminal enhances activity against Gram-positive bacteria. Additionally, assays to quantify reactive oxygen species (ROS) generation and cell viability were performed using a series of nine jadomycins. Compound 1 was found to produce the highest ROS activity and to possess the greatest cytotoxicity against MDA-MB-231 breast cancer cells.

AB - Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1) obtained from a culture of S. venezuelae ISP5230 with L-ornithine (Orn). 1 arises from the rearrangement of a putative five-membered ring containing jadomycin incorporating Orn, whereby intramolecular attack of the E-ring carbonyl from the δ-NH2 group of the Orn side chain results in collapse of the oxazolone ring and formation of a stable six-membered lactam. This rearrangement produces a jadomycin with a 3a hemiaminal position that is susceptible to solvolysis. A structure-activity relationship is discussed based on the antimicrobial activity of 1 compared to previously reported jadomycins, providing evidence that the presence of a 3a hemiaminal enhances activity against Gram-positive bacteria. Additionally, assays to quantify reactive oxygen species (ROS) generation and cell viability were performed using a series of nine jadomycins. Compound 1 was found to produce the highest ROS activity and to possess the greatest cytotoxicity against MDA-MB-231 breast cancer cells.

KW - Anti-Bacterial Agents/pharmacology

KW - Antineoplastic Agents/pharmacology

KW - Cell Line, Tumor

KW - Cell Survival/drug effects

KW - Drug Resistance, Neoplasm

KW - Humans

KW - Isoquinolines/chemistry

KW - Microbial Sensitivity Tests

KW - Ornithine/chemistry

KW - Reactive Oxygen Species/metabolism

KW - Staphylococcus/drug effects

KW - Streptomyces/metabolism

KW - Structure-Activity Relationship

KW - Triple Negative Breast Neoplasms/drug therapy

U2 - 10.1038/s41429-018-0060-0

DO - 10.1038/s41429-018-0060-0

M3 - Journal article

C2 - 29700425

VL - 71

SP - 722

EP - 730

JO - The Journal of antibiotics

JF - The Journal of antibiotics

SN - 0021-8820

IS - 8

ER -