Antiplasmodial activity and in vivo bio-distribution of chloroquine molecules released with a 4-(4-ethynylphenyl)-triazole moiety from organometallo-cobalamins

Rossier, Jeremie, Sovari, Sara Nasiri, Pavic, Aleksandar, Vojnovic, Sandra, Stringer, Tameryn ORCID: https://orcid.org/0000-0002-4439-131X, Bättig, Sarah, Smith, Gregory S., Nikodinovic-Runic, Jasmina and Zobi, Fabio (2019) Antiplasmodial activity and in vivo bio-distribution of chloroquine molecules released with a 4-(4-ethynylphenyl)-triazole moiety from organometallo-cobalamins. Molecules, 24 (12). ISSN 1420-3049

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Abstract

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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Chemistry
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Depositing User: LivePure Connector
Date Deposited: 04 Jul 2022 11:30
Last Modified: 12 Aug 2022 05:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/85924
DOI: 10.3390/molecules24122310

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