A Fully Synthetic 6-Aza-artemisinin Bearing an Amphiphilic Chain Generates Aggregates and Exhibits Anti-Cancer Activities

Installation of a nitrogen at the C6 position of artemisinin facilitates the appendage of a functional unit on the cyclohexane moierty (C-ring). In this study, conjugation of an amphiphilic chain, composed of sequentially connected hydrophilic oligoethylene glycol, hydrophobic alkyl chain, urea, and 4,4’-disubstituted biphenyl linker, imparted self-assembling properties. The fully synthetic mid-molecular weights 6-aza-artemisinin 6 bearing the amphiphilic moiety formed aggregates (approx. 200 nm) at ambient temperature and exhibited increased in vitro anti-cancer activities compared to the N-benzylated aza-artemisinin 5.