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Novel unit B cryptophycin analogues as payloads for targeted therapy
Cryptophycins are naturally occurring cytotoxins with great potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the desi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009196/ https://www.ncbi.nlm.nih.gov/pubmed/29977395 http://dx.doi.org/10.3762/bjoc.14.109 |
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author | Figueras, Eduard Borbély, Adina Ismail, Mohamed Frese, Marcel Sewald, Norbert |
author_facet | Figueras, Eduard Borbély, Adina Ismail, Mohamed Frese, Marcel Sewald, Norbert |
author_sort | Figueras, Eduard |
collection | PubMed |
description | Cryptophycins are naturally occurring cytotoxins with great potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. |
format | Online Article Text |
id | pubmed-6009196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-60091962018-07-05 Novel unit B cryptophycin analogues as payloads for targeted therapy Figueras, Eduard Borbély, Adina Ismail, Mohamed Frese, Marcel Sewald, Norbert Beilstein J Org Chem Full Research Paper Cryptophycins are naturally occurring cytotoxins with great potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. Beilstein-Institut 2018-06-01 /pmc/articles/PMC6009196/ /pubmed/29977395 http://dx.doi.org/10.3762/bjoc.14.109 Text en Copyright © 2018, Figueras et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
spellingShingle | Full Research Paper Figueras, Eduard Borbély, Adina Ismail, Mohamed Frese, Marcel Sewald, Norbert Novel unit B cryptophycin analogues as payloads for targeted therapy |
title | Novel unit B cryptophycin analogues as payloads for targeted therapy |
title_full | Novel unit B cryptophycin analogues as payloads for targeted therapy |
title_fullStr | Novel unit B cryptophycin analogues as payloads for targeted therapy |
title_full_unstemmed | Novel unit B cryptophycin analogues as payloads for targeted therapy |
title_short | Novel unit B cryptophycin analogues as payloads for targeted therapy |
title_sort | novel unit b cryptophycin analogues as payloads for targeted therapy |
topic | Full Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009196/ https://www.ncbi.nlm.nih.gov/pubmed/29977395 http://dx.doi.org/10.3762/bjoc.14.109 |
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