Synthesis and biological effect of lysosome-targeting fluorescent anion transporters with enhanced anionophoric activity.
Cathepsin B enzyme
Fluorescent anion transporter
Lysosomal alkalization
Lysosome targeting
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:
01 10 2020
01 10 2020
Historique:
received:
12
05
2020
revised:
28
07
2020
accepted:
31
07
2020
pubmed:
7
8
2020
medline:
22
6
2021
entrez:
7
8
2020
Statut:
ppublish
Résumé
Two lysosome-targeting fluorescent anion transporters derived from coumarins, trifluoromethylated arylsquaramides and morpholines were synthesized, and their specificity and efficiency to target and alkalize lysosomes were investigated. They are able to target lysosomes specifically. Compared with the previous analogue without trifluoromethyl substituents, these two conjugates, in particular the one having a 3,5-bis(trifluoromethyl) substituent, exhibit significantly higher ability to facilitate the transport of chloride anions, alkalize lysosomes and reduce the activity of lysosomal Cathepsin B enzyme. The present finding suggests that improving the anionophoric activity of lysosome-targeting fluorescent anion transporters is favorable to the efficiency to alkalize lysosomes and deactivate lysosomal Cathepsin B enzyme.
Identifiants
pubmed: 32755679
pii: S0960-894X(20)30572-2
doi: 10.1016/j.bmcl.2020.127461
pii:
doi:
Substances chimiques
Chlorides
0
Coumarins
0
Cyclobutanes
0
Morpholines
0
CTSB protein, human
EC 3.4.22.1
Cathepsin B
EC 3.4.22.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127461Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.