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

Abstract

A series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i 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 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than β-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy.

Graphical Abstract

Keywords:

• β-elemene
• hydroxyl carboximate derivatives
• anti-tumour drugs
• lung cancer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project was supported by the National Natural Science Foundation of China, NSFC (Grant No. 82073686, 81730108, and 81973635), Scientific Research Foundation for Scholars of Hangzhou Normal University (2019QDL003), the Ministry of Science and Technology of China (High-end foreign experts program, G20200217005, G2021017004 and G2022017007L), Hangzhou City “115” plan to introduce overseas intelligence projects (20200215 and 20210120).