Cytotoxic profiling of artesunic and betulinic acids and their synthetic hybrid compound on neurons and gliomas
A novel approach to circumvent multidrug resistance is hybridization of natural products in dimers. We analyzed homodimers of two artesunic acid molecules and heterohybrids of artesunic acid and betulin in human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells. Multidrug-resistant cells were not cross-resistant to the novel compounds. Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species.