In the last few years, we have been witnessing an increasing interest in ionic liquids (ILs) and organic salts, given their potential applications in biological and pharmaceutical sciences. We report the synthesis and in vitro evaluation of novel organic salts combining betulinate, known for its anticancer properties, with antimalarial drugs, primaquine, chloroquine, and mepacrine, and also with the trihexyltetradecylphosphonium ([P 6,6,6,14 ]) cation. The salts were screened for their in vitro activity against tumor lines HepG2 (liver), MG63 (osteosarcoma), T47D (breast), A459 (lung), and RKO (colon), and also on normal human fibroblasts. All betulinates prepared displayed antiproliferative properties, with the trihexyltetradecylphosphonium betulinate standing out for its higher selectivity. This unprecedented disclosure of a betulinic acid (BA)-derived IL with selective antitumor activity constitutes a relevant first step toward development of novel anticancer therapies based on BA-derived IL. (1) Ferraz, R.; Branco, L. C.; Marrucho, I. M.; Araujo, J. M. M.; Rebelo, L. P. N.; da Ponte, M. N.; Prudencio, C.; Noronha, J. P.; Petrovski, Z. Development of novel ionic liquids based on ampicillin. MedChemComm 2012, 3, 494−497. (2) Ferraz, R.; Branco, L. C.; Prudencio, C.; Noronha, J. P.; Petrovski, Z. Ionic Liquids as Active Pharmaceutical Ingredients. ChemMedChem 2011, 6, 975−985. (3) Ferraz, R.; Costa-Rodrigues, J.; Fernandes, M. H.; Santos, M. M.; Marrucho, I. M.; Rebelo, L. P. N.; Prudencio, C.; Noronha, J. P.; Petrovski, Z.; Branco, L. C. Antitumor Activity of Ionic Liquids Based on Ampicillin.
