Design, synthesis and biological evaluation of novel sesquiterpene mustards as potential anticancer agents

European Journal of Medicinal Chemistry
Yuan-Zhen XuKun Gao

Abstract

Several novel series of sesquiterpene mustards (SMs) bearing nitrogen mustard and glutathione (GSH)-reactive α-methylene-γ-butyrolactone groups were successfully prepared for the first time and showed excellent antiproliferative activities in vitro. Among them, compounds 2e and 2g displayed the highest antiproliferative properties with IC50 values ranging from 2.5 to 8.7 μM. The selectivity of these two compounds was evaluated by SRB method against human cancer and normal hepatic cells (HepG2 and L02). The induction of apoptosis and effects on the cell cycle distribution with compounds 2e and 2g were investigated by Hoechst 33,258 staining and flow cytometry, which exhibited that they could induce selective cell apoptosis and cell cycle arrest in HepG2 and L02 cells. In addition, further investigation showed that compounds 2e and 2g could obviously inhibit the proliferation of HepG2 cells by inducing significant DNA cross-linking and depleting GSH in cell media. The good cytotoxicity and selectivity of compounds 2e and 2g pointed them as promising leads for anticancer drug design.

References

Apr 1, 1989·Journal of Medicinal Chemistry·F M ArcamoneN Mongelli
Feb 1, 1995·Mutation Research·D W FairbairnK L O'Neill
Mar 28, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·C P AndersonC P Reynolds
Apr 28, 2000·Phytochemistry·D E WedgeF A Macías
Nov 23, 2000·Journal of Agricultural and Food Chemistry·F A MacíasR F Velasco
Dec 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Z Z HuangS C Lu
Dec 24, 2002·Japanese Journal of Cancer Research : Gann·Jung-Hye ChoiKyung-Tae Lee
Jan 6, 2005·Journal of the American Chemical Society·Hatsuo MaedaNorio Itoh
Mar 10, 2005·Bioorganic & Medicinal Chemistry·Laurie L ParkerJohn A Hartley
Oct 11, 2005·Mayo Clinic Proceedings·S Vincent Rajkumar, Robert A Kyle
Sep 2, 2006·Bioorganic & Medicinal Chemistry Letters·Anke BachelierChristian D Klein
Apr 22, 2008·Bioorganic & Medicinal Chemistry·Bastien ReuxPascal Coudert
Sep 18, 2008·Molecular Aspects of Medicine·Henry Jay FormanAlessandra Rinna
Feb 13, 2009·European Journal of Medicinal Chemistry·Andréia Lilian Formento NavariniTânia Beatriz Creczynski-Pasa
Jan 21, 2010·Immunologic Research·Robert A Brodsky
Nov 1, 2011·Journal of the American Chemical Society·Yunyan KuangXiaohua Peng
Mar 19, 2013·European Journal of Medicinal Chemistry·Caroline SchomburgThomas J Schmidt

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Citations

Nov 20, 2016·Journal of Labelled Compounds & Radiopharmaceuticals·Jianguo LinShanshan Wang
Jun 13, 2017·Journal of Agricultural and Food Chemistry·Bruna P da SilvaFrancisco A Macías
Jan 9, 2016·Chemistry : a European Journal·Lucia CerisoliArianna Quintavalla

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