Novel hybrids of natural β-elemene bearing isopropanolamine moieties: synthesis, enhanced anticancer profile, and improved aqueous solubility

Chen, Jichao; Wang, Tianyu; Xu, Shengtao; Aijun, Lin; Yao, Hequan; Xie, Weijia; Zhu, Zheying; Xu, Jinyi

Abstract

A series of novel β-elemene isopropanolamine derivatives were synthesized and evaluated for their antitumor activity. The results indicated that all of the compounds showed stronger antiproliferative activities than β-elemene as well as improved aqueous solubility. In particular dimer 6q showed the strongest cytotoxicity against four tumor cell lines (SGC-7901, HeLa, U87 and A549) with IC50 values ranging from 4.37 to 10.20 μM. Moreover, combination of 6q with cisplatin exhibited a synergistic effect on these cell lines with IC50 values ranging from 1.21 to 2.94 μM, and reversed the resistance of A549/DPP cells with an IC50 value of 2.52 μM. The mechanism study revealed that 6q caused cell cycle arrest at the G2 phase and induced apoptosis of SGC-7901 cells through a mitochondrial-dependent apoptotic pathway. Further in vivo study in H22 liver cancer xenograft mouse model validated the antitumor activity of 6q with a tumor inhibitory ratio (TIR) of 60.3%, which was higher than that of β-elemene (TIR, 49.1%) at a dose of 60 mg/kg. Altogether, the potent antitumor activity of 6qin vitro and in vivo warranted further preclinical investigation for potential anticancer chemotherapy.

Citation

Chen, J., Wang, T., Xu, S., Aijun, L., Yao, H., Xie, W., …Xu, J. (2017). Novel hybrids of natural β-elemene bearing isopropanolamine moieties: synthesis, enhanced anticancer profile, and improved aqueous solubility. Fitoterapia, 120, https://doi.org/10.1016/j.fitote.2017.05.002

• Journal Article Type: Article
• Acceptance Date: May 16, 2017
• Online Publication Date: May 31, 2017
• Publication Date: Jul 1, 2017
• Deposit Date: Jul 4, 2017
• Publicly Available Date: Jul 4, 2017
• Journal: Fitoterapia
• Print ISSN: 0367-326X
• Electronic ISSN: 1873-6971
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 120
• DOI: https://doi.org/10.1016/j.fitote.2017.05.002
• Keywords: β-Elemene; Isopropanolamine; Dimer; Antitumor activity; Aqueous solubility
• Public URL: https://nottingham-repository.worktribe.com/output/967731
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0367326X17301429
• Contract Date: Jul 4, 2017