Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells

Four neoantimycins H-K (1–4) with C1-keto, including the new ones (1–2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5–8) in vitro, the absolute structures of 1–8 were established/reconfirmed by analyz...

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Autores principales: Lin, Xiao, Zhou, Yongjun, Liu, Liyun, Zhu, Hongrui, Chen, Yeping, Wang, Shuping, Sun, Fan, Chai, Ling, Liu, Buming, Xu, Shihai, Lin, Hou-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624652/
https://www.ncbi.nlm.nih.gov/pubmed/31334224
http://dx.doi.org/10.3389/fchem.2019.00481
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author Lin, Xiao
Zhou, Yongjun
Liu, Liyun
Zhu, Hongrui
Chen, Yeping
Wang, Shuping
Sun, Fan
Chai, Ling
Liu, Buming
Xu, Shihai
Lin, Hou-Wen
author_facet Lin, Xiao
Zhou, Yongjun
Liu, Liyun
Zhu, Hongrui
Chen, Yeping
Wang, Shuping
Sun, Fan
Chai, Ling
Liu, Buming
Xu, Shihai
Lin, Hou-Wen
author_sort Lin, Xiao
collection PubMed
description Four neoantimycins H-K (1–4) with C1-keto, including the new ones (1–2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5–8) in vitro, the absolute structures of 1–8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.
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spelling pubmed-66246522019-07-22 Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells Lin, Xiao Zhou, Yongjun Liu, Liyun Zhu, Hongrui Chen, Yeping Wang, Shuping Sun, Fan Chai, Ling Liu, Buming Xu, Shihai Lin, Hou-Wen Front Chem Chemistry Four neoantimycins H-K (1–4) with C1-keto, including the new ones (1–2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5–8) in vitro, the absolute structures of 1–8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably. Frontiers Media S.A. 2019-07-05 /pmc/articles/PMC6624652/ /pubmed/31334224 http://dx.doi.org/10.3389/fchem.2019.00481 Text en Copyright © 2019 Lin, Zhou, Liu, Zhu, Chen, Wang, Sun, Chai, Liu, Xu and Lin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Lin, Xiao
Zhou, Yongjun
Liu, Liyun
Zhu, Hongrui
Chen, Yeping
Wang, Shuping
Sun, Fan
Chai, Ling
Liu, Buming
Xu, Shihai
Lin, Hou-Wen
Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title_full Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title_fullStr Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title_full_unstemmed Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title_short Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells
title_sort compound discovery and structure-activity relationship study of neoantimycins against drug-resistant cancer cells
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624652/
https://www.ncbi.nlm.nih.gov/pubmed/31334224
http://dx.doi.org/10.3389/fchem.2019.00481
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