Article (Scientific journals)
Structure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities.
Leverrier, Aurelie; Bero, Joanne; Cabrera, Julian et al.
2015In European Journal of Medicinal Chemistry, 100, p. 10-7
Peer Reviewed verified by ORBi
 

Files


Full Text
Hybrids_cinchona_reprint.pdf
Publisher postprint (488.42 kB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Antiparasitic activity; Barton-Zard reaction; Bile acids; Cinchona alkaloids; Hybrids
Abstract :
[en] In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids were prepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a covalent C-C bond via a decarboxylative Barton-Zard reaction between the two entities. The bile acids showed only weak antiparasitic properties, but all the hybrids exhibited high in vitro activities (IC50: 0.48-5.39 muM) against Trypanosoma brucei. These hybrids were more active than their respective parent alkaloids (up to a 135 fold increase in activity), and displayed good selectivity indices. Aditionally, all these compounds inhibited the in vitro growth of a chloroquine-sensitive strain of Plasmodium falciparum (3D7: IC50: 36.1 nM to 8.72 muM), and the most active hybrids had IC50s comparable to that of artemisinin (IC50: 36 nM). Some structure-activity relationships among the group of 48 hybrids are discussed. The increase in antiparasitic activity may be explained by an improvement in bioavailability, since the more lipophilic derivatives showed the lowest IC50s.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Leverrier, Aurelie
Bero, Joanne
Cabrera, Julian
Frederich, Michel  ;  Université de Liège - ULiège
Quetin-Leclercq, Joelle
Palermo, Jorge A.
Language :
English
Title :
Structure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities.
Publication date :
2015
Journal title :
European Journal of Medicinal Chemistry
ISSN :
0223-5234
eISSN :
1768-3254
Publisher :
Elsevier, Netherlands
Volume :
100
Pages :
10-7
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 Elsevier Masson SAS. All rights reserved.
Available on ORBi :
since 13 October 2015

Statistics


Number of views
43 (0 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
 
17
Scopus citations®
without self-citations
15
OpenCitations
 
10

Bibliography


Similar publications



Contact ORBi