Second generation β-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma

Abstract

Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, β-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour efficacy. To improve the anti-tumour activity of β-elemene, based on its minor molecular weight character, we introduced furoxan nitric oxide (NO) donors into the β-elemene structure and designed six series of new generation β-elemene NO donor hybrids. The synthesised compounds could effectively release NO <i>in vitro</i>, displayed significant anti-proliferative effects on U87MG, NCI-H520, and SW620 cell lines. In the orthotopic glioma model, compound <b>Id</b> significantly and continuously suppressed the growth of gliomas in nude mice, and the brain glioma of the treatment group was markedly inhibited (>90%). In short, the structural fusion design of NO donor and β-elemene is a feasible strategy to improve the <i>in vivo</i> anti-tumour activity of β-elemene.