Next Article in Journal
Improved Methods for Treatment of Phytopathogenic Biofilms: Metallic Compounds as Anti-Bacterial Coatings and Fungicide Tank-Mix Partners
Next Article in Special Issue
Evaluation of Elastin-Like Polypeptides for Tumor Targeted Delivery of Doxorubicin to Glioblastoma
Previous Article in Journal
The Influence of Solution pH on the Kinetics of Resorcinol Electrooxidation (Degradation) on Polycrystalline Platinum
Open AccessArticle

Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins

1
Department of Chemistry, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland
2
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Republic of Serbia
3
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Rafik Karaman
Molecules 2019, 24(12), 2310; https://doi.org/10.3390/molecules24122310
Received: 28 May 2019 / Revised: 17 June 2019 / Accepted: 19 June 2019 / Published: 21 June 2019
(This article belongs to the Special Issue Prodrugs and Their Future Prospects and Clinical Impact)
We have explored the possibility of using organometallic derivatives of cobalamin as a scaffold for the delivery of the same antimalarial drug to both erythro- and hepatocytes. This hybrid molecule approach, intended as a possible tool for the development of multi-stage antimalarial agents, pivots on the preparation of azide-functionalized drugs which, after coupling to the vitamin, are released with a 4-(4-ethynylphenyl)-triazole functionality. Three chloroquine and one imidazolopiperazine derivative (based on the KAF156 structure) were selected as model drugs. One hybrid chloroquine conjugate was extensively studied via fluorescent labelling for in vitro and in vivo bio-distribution studies and gave proof-of-concept for the design. It showed no toxicity in vivo (zebrafish model) as well as no hepatotoxicity, no cardiotoxicity or developmental toxicity of the embryos. All 4-(4-ethynylphenyl)-triazole derivatives of chloroquine were equally active against chloroquine-resistant (CQR) and chloroquine-sensitive (CQS) Plasmodium falciparum strains. View Full-Text
Keywords: antimalarial; prodrug; chloroquine; triazole; cobalamin; in vivo; zebrafish model antimalarial; prodrug; chloroquine; triazole; cobalamin; in vivo; zebrafish model
Show Figures

Figure 1

MDPI and ACS Style

Rossier, J.; Nasiri Sovari, S.; Pavic, A.; Vojnovic, S.; Stringer, T.; Bättig, S.; Smith, G.S.; Nikodinovic-Runic, J.; Zobi, F. Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins. Molecules 2019, 24, 2310.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop