Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

[Image: see text] The arimetamycin A glycan governs the compound’s cytotoxicity (IC(50)). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubi...

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Autores principales: Huseman, Eric D., Byl, Jo Ann W., Chapp, Scott M., Schley, Nathan D., Osheroff, Neil, Townsend, Steven D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393218/
https://www.ncbi.nlm.nih.gov/pubmed/34471677
http://dx.doi.org/10.1021/acscentsci.1c00040
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author Huseman, Eric D.
Byl, Jo Ann W.
Chapp, Scott M.
Schley, Nathan D.
Osheroff, Neil
Townsend, Steven D.
author_facet Huseman, Eric D.
Byl, Jo Ann W.
Chapp, Scott M.
Schley, Nathan D.
Osheroff, Neil
Townsend, Steven D.
author_sort Huseman, Eric D.
collection PubMed
description [Image: see text] The arimetamycin A glycan governs the compound’s cytotoxicity (IC(50)). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubicinone. The result of the approach was a synthesis of arimetamycin A and two novel hybrid anthracyclines. Each molecule exhibited enhanced cytotoxicity in comparison to the parent anthracyclines, steffimycin B, daunorubicin, and doxorubicin. An orienting mechanistic evaluation revealed that the daunorubicin hybrid inhibits the ability of human topoisomerase IIα to relax negatively and positively supercoiled DNA.
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spelling pubmed-83932182021-08-31 Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids Huseman, Eric D. Byl, Jo Ann W. Chapp, Scott M. Schley, Nathan D. Osheroff, Neil Townsend, Steven D. ACS Cent Sci [Image: see text] The arimetamycin A glycan governs the compound’s cytotoxicity (IC(50)). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubicinone. The result of the approach was a synthesis of arimetamycin A and two novel hybrid anthracyclines. Each molecule exhibited enhanced cytotoxicity in comparison to the parent anthracyclines, steffimycin B, daunorubicin, and doxorubicin. An orienting mechanistic evaluation revealed that the daunorubicin hybrid inhibits the ability of human topoisomerase IIα to relax negatively and positively supercoiled DNA. American Chemical Society 2021-07-22 2021-08-25 /pmc/articles/PMC8393218/ /pubmed/34471677 http://dx.doi.org/10.1021/acscentsci.1c00040 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Huseman, Eric D.
Byl, Jo Ann W.
Chapp, Scott M.
Schley, Nathan D.
Osheroff, Neil
Townsend, Steven D.
Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title_full Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title_fullStr Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title_full_unstemmed Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title_short Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
title_sort synthesis and cytotoxic evaluation of arimetamycin a and its daunorubicin and doxorubicin hybrids
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393218/
https://www.ncbi.nlm.nih.gov/pubmed/34471677
http://dx.doi.org/10.1021/acscentsci.1c00040
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