Original scientific paper

https://doi.org/10.2478/acph-2018-0039

Chloroquine urea derivatives: synthesis and antitumor activity in vitro

KRISTINA PAVIĆ ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, HR-10 000 Zagreb, Croatia
ZRINKA RAJIĆ ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, HR-10 000 Zagreb, Croatia
ZVONIMIR MLINARIĆ orcid.org/0000-0003-2571-2461 ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, HR-10 000 Zagreb, Croatia
LIDIJA UZELAC orcid.org/0000-0002-3076-7064 ; Rudjer Bošković Institute, Division of Molecular Medicine, Laboratory of Experimental Therapy, HR-10 000 Zagreb, Croatia
MARIJETA KRALJ ; Rudjer Bošković Institute, Division of Molecular Medicine, Laboratory of Experimental Therapy, HR-10 000 Zagreb, Croatia
BRANKA ZORC orcid.org/0000-0003-4355-8816 ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, HR-10 000 Zagreb, Croatia

Abstract

In the current paper, we describe design, synthesis and antiproliferative screening of novel chloroquine derivatives with a quinoline core linked to a hydroxy or halogen amine through a flexible aminobutyl chain and urea spacer. Synthetic pathway leading to chloroquine urea derivatives 4-10 includes two crucial steps: i) synthesis of chloroquine benzotriazolide 3 and ii) formation of the urea derivatives through the reaction of compound 3 with the corresponding amine. Testing of antiproliferative activity against four human cancer cell lines revealed that chloroquine urea derivatives 9 and 10 with aromatic moieties show activity in micromolar concentrations. Therefore, these molecules represent interesting lead compounds that might provide insight into the design of new anticancer agents.

Keywords

chloroquine; hydroxychloroquine; urea; antitumor activity in vitro

Hrčak ID:

203273

URI

https://hrcak.srce.hr/203273

Publication date:

31.12.2018.

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