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

Chen, Jichao and Wang, Tianyu and Xu, Shengtao and Aijun, Lin and Yao, Hequan and Xie, Weijia and Zhu, Zheying and Xu, Jinyi (2017) Novel hybrids of natural β-elemene bearing isopropanolamine moieties: synthesis, enhanced anticancer profile, and improved aqueous solubility. Fitoterapia, 120 . pp. 127-125. ISSN 1873-6971

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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.

Item Type: Article
Keywords: β-Elemene; Isopropanolamine; Dimer; Antitumor activity; Aqueous solubility
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1016/j.fitote.2017.05.002
Depositing User: Zhu, Zheying
Date Deposited: 04 Jul 2017 07:24
Last Modified: 13 Aug 2017 15:59
URI: http://eprints.nottingham.ac.uk/id/eprint/43894

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