Rossier, Jeremie Sovari, Sara Nasiri Pavic, Aleksandar Vojnovic, Sandra Stringer, Tameryn Bättig, Sarah Smith, Gregory S. Nikodinovic-Runic, Jasmina Zobi, Fabio 2019-06-21 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. application/pdf https://folia.unifr.ch/global/documents/308086 https://folia.unifr.ch/documents/308086/files/zob_aav.pdf https://folia.unifr.ch/documents/308086/files/zob_aav_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules24122310 info:eu-repo/semantics/openAccess License undefined Molecules. - 2019, vol. 24, no. 12, p. 2310 info:eu-repo/classification/udc/54 Antiplasmodial activity and in vivo bio-distribution of chloroquine molecules released with a 4-(4-ethynylphenyl)-triazole moiety from organometallo-cobalamins http://purl.org/coar/resource_type/c_6501