Acta Pharm. 68 (2018) 471-483

 

full paper

Original research paper

 

Cloroquine urea derivatives: synthesis and antitumor activity in vitro

KRISTINA PAVIĆ, ZRINKA RAJIĆ, ZVONIMIR MLINARIĆ, LIDIJA UZELAC, MARIJETA KRALj and BRANKA ZORC

bzorc@pharma.hr

1 University of Zagreb Faculty of Pharmacy Zagreb, Department of Medicinal Chemistry, HR-10 000 Zagreb, Croatia

2 Rudjer Bošković Institute, Division of Molecular Medicine, Laboratory of Experimental Therapy, HR-10 000 Zagreb, Croatia

Accepted September 11, 2018

Published online September 14, 2018

 

In the current paper, we describe the 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 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 at micromolar concentrations. Therefore, these molecules represent interesting lead compounds that might provide an insight into the design of new anticancer agents.

 

Keywords: chloroquine, hydroxychloroquine, urea, antitumor activity in vitro