Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent.
Anti-cancer agents
NRP-a308 stability
NRPa-308 synthesis
Neuropilins
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 12 2019
15 12 2019
Historique:
received:
15
07
2019
accepted:
17
09
2019
pubmed:
9
11
2019
medline:
25
9
2020
entrez:
9
11
2019
Statut:
ppublish
Résumé
We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation. Nevertheless, we succeeded a gram scale synthesis, according to an expeditious three steps route, without intermediate purification. This latter point is of utmost interest in reducing the ecologic impact and production costs in the perspective of further scale-up processes. The purity of NRPa-308 has been attested by means of conventional structural analyses and its crystallisation allowed a structural assessment by X-Ray diffraction. We also reported the remarkable chemical stability of this molecule in acidic, neutral and basic aqueous media. Eventually, we observed for the first time the accumulation of NRPa-308 in two types of human breast cancer cells MDA-MB231 and BT549.
Identifiants
pubmed: 31699610
pii: S0960-894X(19)30668-7
doi: 10.1016/j.bmcl.2019.126710
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Neuropilin-1
144713-63-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126710Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.