Concise Synthesis of Tunicamycin V and Discovery of a Cytostatic DPAGT1 Inhibitor.
Antimigration Effect
Cytostatic Activity
DPAGT1 Inhibitors
Total Synthesis
Tunicamycins
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
received:
02
03
2022
pubmed:
21
5
2022
medline:
27
7
2022
entrez:
20
5
2022
Statut:
ppublish
Résumé
A short total synthesis of tunicamycin V (1), a non-selective phosphotransferase inhibitor, is achieved via a Büchner-Curtius-Schlotterbeck type reaction. Tunicamycin V can be synthesized in 15 chemical steps from D-galactal with 21 % overall yield. The established synthetic scheme is operationally very simple and flexible to introduce building blocks of interest. The inhibitory activity of one of the designed analogues 28 against human dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1) is 12.5 times greater than 1. While tunicamycins are cytotoxic molecules with a low selectivity, the novel analogue 28 displays selective cytostatic activity against breast cancer cell lines including a triple-negative breast cancer.
Identifiants
pubmed: 35594368
doi: 10.1002/anie.202203225
pmc: PMC9329268
mid: NIHMS1810035
doi:
Substances chimiques
Antineoplastic Agents
0
Cytostatic Agents
0
Tunicamycin
11089-65-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202203225Subventions
Organisme : NCI NIH HHS
ID : R01 CA229164
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114611
Pays : United States
Informations de copyright
© 2022 Wiley-VCH GmbH.
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