Novel hydroxyl carboximates derived from -elemene: design, synthesis and anti-tumour activities evaluation.

A series of novel -alkyl--hydroxyl carboximates derived from -elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound -elemene (). Notably, compound exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound could significantly induce cell apoptosis. Further study in the H460 xenograft mouse model validated the anti-tumour activities of with a greater tumour growth inhibition (TGI, 68.3%) than -elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such -alkyl--hydroxyl carboximate class of compounds exemplified as demonstrated potent anticancer activities both and , and should warrant further investigation for potential anticancer therapy.