Synthesis and biological evaluation of β-lapachone-monastrol hybrids as potential anticancer agents.

European Journal of Medicinal Chemistry
Liqiang WuChong Zhang

Abstract

A series of novel β-lapachone analogs was designed and synthesized by replacing pyran ring of β-lapachone with tetrahydropyrimidinethione moiety of monastrol. These hybrids had potent antiproliferative activity against NQO1-rich cell lines (HepG2 and A549), while NQO1-defficient cell lines (H596 and LO2) were less sensitive to these hybrids. Dicoumarol partially inhibited the activity of these compounds against A549 cell lines, indicating that the activation of biological reduction mediated by NQO1 might partly affect the antiproliferative effects. NQO1 assay and docking study demonstrated 4j was a good substrate of NQO1. Furthermore, as suggested by cellular mechanistic research concerning antitumor activity, the representative compound 4j resulted in ROS production depending on NQO1, then oxidative stress triggered apoptotic cell death. Importantly, 4j significantly suppressed cancer growth in HepG2 xenograft models without obvious toxicity, suggesting that 4j deserve further research as potent antitumor agents for cancer therapy.

References

Jan 1, 1992·Toxicology and Applied Pharmacology·T J MonksD G Graham
Mar 15, 1990·International Journal of Cancer. Journal International Du Cancer·J J Schlager, G Powis
Jan 1, 1987·Pharmacology & Therapeutics·G Powis
Jan 1, 1997·British Journal of Cancer·A MarínJ Bello
Feb 22, 2000·The Journal of Biological Chemistry·J J PinkD A Boothman
Apr 23, 2004·Molecular Pharmacology·David SiegelDavid Ross
Dec 20, 2007·Applied Immunohistochemistry & Molecular Morphology : AIMM·Nida S AwadallahKenneth R Shroyer
Jun 7, 2008·Chemical Communications : Chem Comm·Elizabeth Anne HillardChristian Amatore
Dec 2, 2009·Journal of Medicinal Chemistry·Eufrânio N da SilvaAntônio V Pinto
Mar 23, 2010·Bioorganic & Medicinal Chemistry·Evelyn L BonifaziRosana I Misico
Apr 14, 2011·Organic & Biomolecular Chemistry·David R da RochaVitor F Ferreira
Jan 5, 2013·European Journal of Medicinal Chemistry·Koneni V SashidharaSurendar Reddy Bathula
Feb 26, 2013·European Journal of Medicinal Chemistry·Hala Bakr El-Nassan
Oct 8, 2013·European Journal of Medicinal Chemistry·Solange L de CastroEufrânio N da Silva Júnior
Jun 14, 2016·Current Pharmaceutical Design·Vitor Francisco FerreiraFernando de Carvalho da Silva
Jun 25, 2016·European Journal of Medicinal Chemistry·Eduardo H G da CruzEufrânio N da Silva Júnior
Jul 2, 2017·European Journal of Medicinal Chemistry·Fatma A F RagabMohamed Aboelmagd
May 2, 2018·Journal of Medicinal Chemistry·Kuojun ZhangSheng Jiang
Oct 13, 2018·Chemical Science·Tiago RodriguesGonçalo J L Bernardes
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Danielly C Ferraz da CostaJerson L Silva

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