Antioxidant properties of novel dimers derived from natural ??elemene through inhibiting H2O2?induced apoptosis

Chen, Jichao; Wang, Ruifan; Wang, Tianyu; Ding, Qilong; Khalil, Aliahmad; Xu, Shengtao; Lin, Aijun; Yao, Hequan; Xie, Weijia; Zhu, Zheying; Xu, Jinyi

Abstract

A series of novel ?-elemene dimer derivatives were synthesized and evaluated for their antioxidant activities. The results indicated that most of the target compounds showed more potent cytoprotective effects than positive control vitamin E. In particular, dimer D5 exhibited the strongest antioxidant activity, which was significantly superior to the active compound D1 obtained in our previous study. Besides, D5 did not produce obvious cytotoxicity in normal human umbilical vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by H2O2 in a concentration-dependent manner. Further studies suggested that the cytoprotective action of D5 might be mediated, at least in part, by increasing the intracellular superoxide dismutase activity and nitric oxide secretion as well as decreasing the intracellular malonyldialdehyde content and lactate dehydrogenase release. Furthermore, D5 observably inhibited ROS generation and prevented H2O2-induced apoptosis in HUVECs possibly via inhibiting the activation of the MAPK signaling pathway.

Citation

Chen, J., Wang, R., Wang, T., Ding, Q., Khalil, A., Xu, S., …Xu, J. (in press). Antioxidant properties of novel dimers derived from natural β‑elemene through inhibiting H2O2‑induced apoptosis. ACS Medicinal Chemistry Letters, 8(4), https://doi.org/10.1021/acsmedchemlett.7b00035

• Journal Article Type: Article
• Acceptance Date: Mar 13, 2017
• Online Publication Date: Mar 13, 2017
• Deposit Date: May 17, 2017
• Journal: ACS Medicinal Chemistry Letters
• Print ISSN: 1948-5875
• Electronic ISSN: 1948-5875
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 4
• DOI: https://doi.org/10.1021/acsmedchemlett.7b00035
• Keywords: antioxidant activity; apoptosis; dimer; MAPK pathway; ?-Elemene
• Public URL: https://nottingham-repository.worktribe.com/output/849945
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.7b00035
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters copyright © 2017 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.7b00035