Permeability studies of coumarins with new accelerated Caco-2 cell model

Coumarins are attractive molecules due to their diverse functions and substitution possibilities. Since they are also part of the human diet, it is important to know how they are absorbed. Thus we evaluated the permeability and cytotoxicity of 18 coumarins, with different counting number of OH, CH₃ and OCH₃, groups, with new Caco-2 model in which permeability test is performed with robotic workstation and cells are grown on 96-well plates for seven days. Lucifer yellow rejection 99.2±0.58 indicated proper monolayer formation. All studied coumarins, were rapidly permeated across Caco-2 cell monolayer. Compounds were more permeable apical to basolateral direction than in basolateral to apical direction. No significant difference was observed between days according to t-test. The results indicate that all of the studied coumarins are well absorbed in the lumen and efflux is not limiting the absorption. Type and position of substituents affected more to the permeability than the number of substituents. Five coumarins had an influence on the viability of cells (1<80%, 4>1120%) according to WST-1 test, but that does not seem to have a clear influence on the permeability of the compounds.

Acknowledgements: The European Commission 6th framework program Pro-Kinase Research project no. 503467