Novel unit B cryptophycin analogues as payloads for targeted therapy
Figueras, Eduard ; Borbély, Adina ; Ismail, Mohamed LU
; Frese, Marcel
and Sewald, Norbert
(2018)
In Beilstein Journal of Organic Chemistry
14.
p.1281-1286
- Abstract
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.... (More)
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.
(Less)
- author
- Figueras, Eduard
; Borbély, Adina
; Ismail, Mohamed
LU
; Frese, Marcel
and Sewald, Norbert
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- keywords
- Cryptophycin, Cytotoxic agents, Novel payloads, Tubulin inhibitors, Tumour targeting
- in
- Beilstein Journal of Organic Chemistry
- volume
- 14
- pages
- 6 pages
- publisher
- Beilstein-Institut Zur Forderung der Chemischen Wissenschaften
- external identifiers
-
- scopus:85048224750
- ISSN
- 1860-5397
- DOI
- 10.3762/bjoc.14.109
- language
- English
- LU publication?
- no
- id
- 4ca69113-a041-436b-9f37-5f60d916ec22
- date added to LUP
- 2023-08-28 11:26:37
- date last changed
- 2023-08-29 11:22:20
@article{4ca69113-a041-436b-9f37-5f60d916ec22,
abstract = {{<p>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.</p>}},
author = {{Figueras, Eduard and Borbély, Adina and Ismail, Mohamed and Frese, Marcel and Sewald, Norbert}},
issn = {{1860-5397}},
keywords = {{Cryptophycin; Cytotoxic agents; Novel payloads; Tubulin inhibitors; Tumour targeting}},
language = {{eng}},
pages = {{1281--1286}},
publisher = {{Beilstein-Institut Zur Forderung der Chemischen Wissenschaften}},
series = {{Beilstein Journal of Organic Chemistry}},
title = {{Novel unit B cryptophycin analogues as payloads for targeted therapy}},
url = {{http://dx.doi.org/10.3762/bjoc.14.109}},
doi = {{10.3762/bjoc.14.109}},
volume = {{14}},
year = {{2018}},
}